Research

16 pages, 261 KiB

Open AccessArticle

Remote Physiotherapy for Children with ASD during the COVID-19 Pandemic: A Thematic Analysis of Physical Therapists’ Perspectives

by Yael Harel, Alberto Romano and Meir Lotan

J. Clin. Med. 2024, 13(6), 1610; https://doi.org/10.3390/jcm13061610 - 11 Mar 2024

Viewed by 590

Abstract

Background: Physical therapy plays a crucial role in addressing the physical challenges faced by individuals with autism spectrum disorder (ASD). Amidst the COVID-19 pandemic lockdown, physical therapists (PTs) working in special education centers for ASD children were tasked with deploying remote telehealth [...] Read more.

Background: Physical therapy plays a crucial role in addressing the physical challenges faced by individuals with autism spectrum disorder (ASD). Amidst the COVID-19 pandemic lockdown, physical therapists (PTs) working in special education centers for ASD children were tasked with deploying remote telehealth interventions (RTIs), an uncommon approach in physical therapy until then. The present article aims to describe and discuss the PTs’ perspective of using RTI with children with ASD during the national Israeli COVID-19 lockdown. Methods: Reports from 13 experienced PTs who treated and supported 244 children with ASD using RTIs over six weeks were analyzed. The study employed quantitative research methods, including freely written reports and discussions addressing the question “what were your experiences as a PT treating ASD children remotely during the nationwide COVID-19 lockdown?” Results: the reports were categorized into four main themes: (a) the implications of RTIs on the children; (b) the implications of RTIs on the PTs; (c) modifications for applying RTI; and (d) PTs’ family rapport as a necessary basis for RTI. Noteworthy findings include the unaffected implementation of RTIs by ASD severity level and the dependence of RTI’s success on parental availability and the ability of parents to tailor activities for their child. Conclusions: The findings of the current research suggest that PT services through RTIs are well-suited for individuals with ASD and their families. Full article

(This article belongs to the Special Issue Advances in Autism Spectrum Disorder: Etiopathogenesis, Clinical Phenotypes, Diagnosis and Treatment)

17 pages, 1508 KiB

Open AccessArticle

What Factors Predict Adaptive Functioning in Preschool Children with Autism Spectrum Disorder? A Longitudinal Study

by Laura Casula, Maria Grazia Logrieco, Giulio D’Urso, Silvia Guerrera, Emanuela Petrolo, Ilaria Nicolì, Vittoria Celentano, Giusi Antonia Toto, Stefano Vicari, Mirco Fasolo and Giovanni Valeri

J. Clin. Med. 2024, 13(6), 1565; https://doi.org/10.3390/jcm13061565 - 09 Mar 2024

Viewed by 1391

Abstract

Adaptive functioning constitutes a fundamental aspect of the phenotype associated with autism spectrum disorder (ASD) in preschool-aged children, exerting a significant influence on both the child and the family’s overall quality of life. The aim of this study was to investigate the predictors [...] Read more.

Adaptive functioning constitutes a fundamental aspect of the phenotype associated with autism spectrum disorder (ASD) in preschool-aged children, exerting a significant influence on both the child and the family’s overall quality of life. The aim of this study was to investigate the predictors of the adaptive functioning domains in preschool-age children with ASD at two time points, providing a snapshot of this fundamental developmental step. Methods: Ninety-five children with ASD (M = 3.89, SD = 1.13) were included in the study and longitudinal data (the mean length of the longitudinal data collection was 1 year) on ASD features such as social communication and social interaction, repetitive and restricted behavior, cognitive level, and adaptive functioning were collected. We considered autistic features, cognitive level, and sociodemographic factors as possible predictors of the different adaptive functioning domains one year later. Results: Data obtained showed a worsening of the ASD features and adaptive functioning after one year. Furthermore, the severity of repetitive and restricted behavior predicted adaptive functioning, especially in the social and practical domains of the child, one year later. This prediction was observed alongside the child’s cognitive level. Conclusions: The study identifies some potential predictive factors of specific adaptive functioning domains in preschoolers with ASD. Considering how critical adaptive functioning is for the well-being of both the child and their family, it becomes imperative to design early-stage interventions focused on nurturing adaptive skills in children with ASD. Full article

(This article belongs to the Special Issue Advances in Autism Spectrum Disorder: Etiopathogenesis, Clinical Phenotypes, Diagnosis and Treatment)

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14 pages, 472 KiB

Open AccessArticle

Expression of miRNAs in Pre-Schoolers with Autism Spectrum Disorders Compared with Typically Developing Peers and Its Effects after Probiotic Supplementation

by Letizia Guiducci, Manuela Cabiati, Elisa Santocchi, Margherita Prosperi, Maria Aurora Morales, Filippo Muratori, Emioli Randazzo, Giovanni Federico, Sara Calderoni and Silvia Del Ry

J. Clin. Med. 2023, 12(22), 7162; https://doi.org/10.3390/jcm12227162 - 18 Nov 2023

Viewed by 1070

Abstract

Alteration of the microbiota–gut–brain axis has been recently recognized as a possible contributor to the physiopathology of autism spectrum disorder (ASD). In this context, microRNA (miRNAs) dysfunction, implicated both in several neuropathological conditions including ASD and in different gastrointestinal disorders (GIDs), could represent [...] Read more.

Alteration of the microbiota–gut–brain axis has been recently recognized as a possible contributor to the physiopathology of autism spectrum disorder (ASD). In this context, microRNA (miRNAs) dysfunction, implicated both in several neuropathological conditions including ASD and in different gastrointestinal disorders (GIDs), could represent an important modulating factor. In this contextual framework, we studied the transcriptional profile of specific circulating miRNAs associated with both ASD (miR-197-5p, miR-424-5p, miR-500a-5p, miR-664a-5p) and GID (miR-21-5p, miR-320a-5p, miR-31-5p, miR-223-5p) in a group of pre-schoolers with ASD and in typically developing (TD) peers. In the ASD group, we also assessed the same miRNAs after a 6-month supplementation with probiotics and their correlation with plasma levels of zonulin and lactoferrin. At baseline, the expression of miRNAs involved in ASD were significantly reduced in ASD pre-schoolers vs. TD controls. Regarding the miRNAs involved in GID, the expression levels of miR-320-5p, miR-31-5p, and miR-223-5p were significantly higher in ASD than in TD subjects, whereas miR-21-5p showed significantly reduced expression in the ASD group vs. TD group. Supplementation with probiotics did not significantly change the expression of miRNAs in the ASD population. We found a significative negative correlation between zonulin and miR-197-5p and miR-21-5p at baseline, as well as between lactoferrin and miR-223-5p after 6 months of probiotic supplementation. Our study confirms the presence of an altered profile of the miRNAs investigated in ASD versus TD peers that was not modified by supplementation with probiotics. Full article

(This article belongs to the Special Issue Advances in Autism Spectrum Disorder: Etiopathogenesis, Clinical Phenotypes, Diagnosis and Treatment)

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13 pages, 1432 KiB

Open AccessArticle

Associations between Elemental Metabolic Dynamics and Default Mode Network Functional Connectivity Are Altered in Autism

by Paul Curtin, Janina Neufeld, Austen Curtin, Christine Austin, Johan Isaksson, Karl Lundin Remnelius, Hjalmar Nobel Norrman, Manish Arora and Sven Bölte

J. Clin. Med. 2023, 12(3), 1022; https://doi.org/10.3390/jcm12031022 - 28 Jan 2023

Cited by 1 | Viewed by 1725

Abstract

Autism is a neurodevelopmental condition associated with atypical social communication, cognitive, and sensory faculties. Recent advances in exposure biology suggest that biomarkers of elemental uptake and metabolism measured in hair samples can yield an effective signal predictive of autism diagnosis. Here, we investigated [...] Read more.

Autism is a neurodevelopmental condition associated with atypical social communication, cognitive, and sensory faculties. Recent advances in exposure biology suggest that biomarkers of elemental uptake and metabolism measured in hair samples can yield an effective signal predictive of autism diagnosis. Here, we investigated if elemental biomarkers in hair were associated with functional connectivity in regions of the default mode network (DMN) previously linked to autism. In a study sample which included twin pairs with concordant and discordant diagnoses for autism, our analysis of hair samples and neuroimaging data supported two general findings. First, independent of autism diagnosis, we found a broad pattern of association between elemental biomarkers and functional connectivity in the DMN, which primarily involved dynamics in zinc metabolism. Second, we found that associations between the DMN and elemental biomarkers, particularly involving phosphorus, calcium, manganese, and magnesium, differed significantly in autistic participants from control participants. In sum, these findings suggest that functional dynamics in elemental metabolism relate broadly to persistent patterns of functional connectivity in the DMN, and that these associations are altered in the emergence of autism. Full article

(This article belongs to the Special Issue Advances in Autism Spectrum Disorder: Etiopathogenesis, Clinical Phenotypes, Diagnosis and Treatment)

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10 pages, 289 KiB

Open AccessArticle

Autism Spectrum Disorder May Be Highly Prevalent in People with Functional Neurological Disorders

by Belén González-Herrero, Francesca Morgante, Javier Pagonabarraga, Biba Stanton and Mark J. Edwards

J. Clin. Med. 2023, 12(1), 299; https://doi.org/10.3390/jcm12010299 - 30 Dec 2022

Cited by 4 | Viewed by 5775

Abstract

Recent observations suggest that autism spectrum disorder (ASD) co-occurs in people with a functional neurological disorder (FND), but little systematic data are available on the relationship between FND and autism. The study aimed to assess the self-reported autistic traits via a standardized questionnaire [...] Read more.

Recent observations suggest that autism spectrum disorder (ASD) co-occurs in people with a functional neurological disorder (FND), but little systematic data are available on the relationship between FND and autism. The study aimed to assess the self-reported autistic traits via a standardized questionnaire and the prevalence of previously diagnosed ASD among people with FND and their 1st-degree relatives. We performed a survey of members of the patient organization FNDHope, using a self-completed questionnaire for screening for autistic traits and ASD: the adult autism subthreshold spectrum (AdAS spectrum). There were 344 respondents diagnosed with FND with a mean age of 39.8 ± 11.6 years (female sex 90%). Eight per cent of respondents volunteered a previous diagnosis of ASD, and 24% reported a 1st-degree relative with a formal diagnosis of ASD, mostly their children. We found that 69% of respondents had scores in the AdAS spectrum indicating a clinically significant ASD and 21% indicating autistic traits. Further studies are needed to provide more evidence regarding the prevalence of ASD in people with FND and how this may influence the aetiology, treatment selection and prognosis. Full article

(This article belongs to the Special Issue Advances in Autism Spectrum Disorder: Etiopathogenesis, Clinical Phenotypes, Diagnosis and Treatment)

15 pages, 1705 KiB

Open AccessArticle

Elemental Dynamics in Hair Accurately Predict Future Autism Spectrum Disorder Diagnosis: An International Multi-Center Study

by Christine Austin, Paul Curtin, Manish Arora, Abraham Reichenberg, Austen Curtin, Miyuki Iwai-Shimada, Robert O. Wright, Rosalind J. Wright, Karl Lundin Remnelius, Johan Isaksson, Sven Bölte and Shoji F. Nakayama

J. Clin. Med. 2022, 11(23), 7154; https://doi.org/10.3390/jcm11237154 - 01 Dec 2022

Cited by 3 | Viewed by 14836

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental condition diagnosed in approximately 2% of children. Reliance on the emergence of clinically observable behavioral patterns only delays the mean age of diagnosis to approximately 4 years. However, neural pathways critical to language and social functions [...] Read more.

Autism spectrum disorder (ASD) is a neurodevelopmental condition diagnosed in approximately 2% of children. Reliance on the emergence of clinically observable behavioral patterns only delays the mean age of diagnosis to approximately 4 years. However, neural pathways critical to language and social functions develop during infancy, and current diagnostic protocols miss the age when therapy would be most effective. We developed non-invasive ASD biomarkers using mass spectrometry analyses of elemental metabolism in single hair strands, coupled with machine learning. We undertook a national prospective study in Japan, where hair samples were collected at 1 month and clinical diagnosis was undertaken at 4 years. Next, we analyzed a national sample of Swedish twins and, in our third study, participants from a specialist ASD center in the US. In a blinded analysis, a predictive algorithm detected ASD risk as early as 1 month with 96.4% sensitivity, 75.4% specificity, and 81.4% accuracy (n = 486; 175 cases). These findings emphasize that the dynamics in elemental metabolism are systemically dysregulated in autism, and these signatures can be detected and leveraged in hair samples to predict the emergence of ASD as early as 1 month of age. Full article

(This article belongs to the Special Issue Advances in Autism Spectrum Disorder: Etiopathogenesis, Clinical Phenotypes, Diagnosis and Treatment)

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19 pages, 638 KiB

Open AccessArticle

Expectations and Concerns about the Use of Telemedicine for Autism Spectrum Disorder: A Cross-Sectional Survey of Parents and Healthcare Professionals

by Alessandra Gabellone, Lucia Marzulli, Emilia Matera, Maria Giuseppina Petruzzelli, Anna Margari, Orazio Valerio Giannico and Lucia Margari

J. Clin. Med. 2022, 11(12), 3294; https://doi.org/10.3390/jcm11123294 - 08 Jun 2022

Cited by 8 | Viewed by 2189

Abstract

Telemedicine has recently been used for diagnosis and interventions inpatients with autism spectrum disorder (ASD), traditionally performed in-person, but little attention has been paid to user expectations prior to its use. The aim of this study is to compare the expectations and concerns [...] Read more.

Telemedicine has recently been used for diagnosis and interventions inpatients with autism spectrum disorder (ASD), traditionally performed in-person, but little attention has been paid to user expectations prior to its use. The aim of this study is to compare the expectations and concerns of 50 healthcare professionals and 45 parents of children with ASD regarding the use of telemedicine for diagnostic or treatment purposes. Parents have higher expectations for the use of telemedicine as an alternative (p = 0.0223) and supplement (p = 0.0061) to in-person diagnosis of ASD, as well as a supplement to traditional intervention (p ≤ 0.0001). In addition, while they also have greater hope for improvement in family routines (p = 0.0034) and parenting skills in child management (p = 0.0147), they express greater concern about the need for active parental involvement/supervision during telemedicine services (p = 0.015) and changes in the behaviour of the child with ASD during telemedicine services (p = 0.049). On the other hand, healthcare professionals are more concerned about barriers such as lack of devices (p = 0.000), unfamiliarity with the technology (p = 0.000), poor quality of internet connection (p = 0.006), and severity of ASD (p = 0.000). To achieve promising healthcare for ASD patients, the telemedicine service should try to meet the needs and preferences of both healthcare professionals and parents, as well as identify and, if possible, reduce perceived barriers. Full article

(This article belongs to the Special Issue Advances in Autism Spectrum Disorder: Etiopathogenesis, Clinical Phenotypes, Diagnosis and Treatment)

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11 pages, 274 KiB

Open AccessArticle

Methylphenidate Use for Emotional Dysregulation in Children and Adolescents with ADHD and ADHD and ASD: A Naturalistic Study

by Patrizia Ventura, Concetta de Giambattista, Paolo Trerotoli, Maddalena Cavone, Alessandra Di Gioia and Lucia Margari

J. Clin. Med. 2022, 11(10), 2922; https://doi.org/10.3390/jcm11102922 - 22 May 2022

Cited by 3 | Viewed by 3410

Abstract

Emotional dysregulation (ED) is common in attention-deficit/hyperactivity disorder (ADHD). Nonetheless, research on ADHD in children with autism spectrum disorder (ASD) and ADHD is still ongoing. Several studies suggest that methylphenidate (MPH) may be effective for ED in ADHD, while there is not enough [...] Read more.

Emotional dysregulation (ED) is common in attention-deficit/hyperactivity disorder (ADHD). Nonetheless, research on ADHD in children with autism spectrum disorder (ASD) and ADHD is still ongoing. Several studies suggest that methylphenidate (MPH) may be effective for ED in ADHD, while there is not enough evidence about its use in ASD with comorbid ADHD. This naturalistic study aims to investigate the effectiveness of immediate- and extended-release MPH in the treatment of ED in 70 children and adolescents (6–18 years), with a diagnosis of ADHD (n = 41) and of ASD with comorbid ADHD (n = 29), using the Child Behavior Checklist—Attention/Aggressive/Anxious (CBCL-AAA). Their parents completed the CBCL twice—first during the summer medication-free period, that is, at least one month after drug interruption; and again after three months of treatment restart. Results demonstrate that MPH is associated with a statistically significant reduction in ED in ADHD and ASD, without substantial adverse events, supporting the use of psychostimulants for the treatment of ED in these neurodevelopmental disorders. Full article

(This article belongs to the Special Issue Advances in Autism Spectrum Disorder: Etiopathogenesis, Clinical Phenotypes, Diagnosis and Treatment)

27 pages, 2892 KiB

Open AccessArticle

Research into the Association of Cadmium and Manganese Excretion with Thyroid Function and Behavioral Areas in Adolescents with Autism Spectrum Disorders

by Anna Błażewicz, Ewelina Grywalska, Paweł Macek, Paulina Mertowska, Sebastian Mertowski, Julia Wojnicka, Nicolo Durante and Agata Makarewicz

J. Clin. Med. 2022, 11(3), 579; https://doi.org/10.3390/jcm11030579 - 24 Jan 2022

Cited by 7 | Viewed by 3274

Abstract

Thyroid dysfunction and toxic metal exposure have been linked to the increased risk of autism spectrum disorders (ASD); however, the relationship between those factors remains unclear. We aimed to evaluate the relationship between the serum level of hormones, namely thyroid-stimulating hormone (TSH), free [...] Read more.

Thyroid dysfunction and toxic metal exposure have been linked to the increased risk of autism spectrum disorders (ASD); however, the relationship between those factors remains unclear. We aimed to evaluate the relationship between the serum level of hormones, namely thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), and urinary cadmium (U-Cd) and urinary manganese (U-Mn), in patients with ASD. The study group consisted of 129 adolescents with ASD, and the control group consisted of 86 healthy persons. Ion chromatography with spectrophotometric detection (IC-UV/ViS) was used to quantitatively determine Cd and Mn in all 24-h urine samples. These results indicate that severity of certain symptoms in autism is associated with thyroid function. Correlation analysis between Childhood Autism Rating Scale (CARS) results and the content of both U-Mn and U-Cd as well as fT3, fT4 and TSH values in ASD patients showed significantly positive correlation of CARS7 (visual reaction) with fT3 and fT4 and a negative correlation with TSH for the whole study group. In the group of adolescents over 14 years of age, it was also observed that CARS10 (anxiety reaction) negatively correlates with serum TSH levels, and among younger individuals, CARS9 (near receptor responsiveness, taste, smell) positively correlates with TSH. Full article

(This article belongs to the Special Issue Advances in Autism Spectrum Disorder: Etiopathogenesis, Clinical Phenotypes, Diagnosis and Treatment)

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14 pages, 948 KiB

Open AccessArticle

Implicit and Explicit Memory in Youths with High-Functioning Autism Spectrum Disorder: A Case-Control Study

by Elisa Fucà, Giulia Lazzaro, Floriana Costanzo, Silvia Di Vara, Deny Menghini and Stefano Vicari

J. Clin. Med. 2021, 10(18), 4283; https://doi.org/10.3390/jcm10184283 - 21 Sep 2021

Cited by 1 | Viewed by 2223

Abstract

Individuals with autism spectrum disorder (ASD) usually manifest heterogeneous impairments in their higher cognitive functions, including their implicit memory (IM) and explicit memory (EM). However, the findings on IM and EM in youths with ASD remain debated. The aim of this study was [...] Read more.

Individuals with autism spectrum disorder (ASD) usually manifest heterogeneous impairments in their higher cognitive functions, including their implicit memory (IM) and explicit memory (EM). However, the findings on IM and EM in youths with ASD remain debated. The aim of this study was to clarify such conflicting results by examining IM and EM using two comparable versions of the Serial Reaction Time Task (SRTT) in the same group of children and adolescents with ASD. Twenty-five youths with high-functioning ASD and 29 age-matched and IQ-matched typically developing youths undertook both tasks. The ability to implicitly learn the temporal sequence of events across the blocks in the SRTT was intact in the youths with ASD. When they were tested for EM, the participants with ASD did not experience a significant reduction in their reaction times during the blocks with the previously learned sequence, suggesting an impairment in EM. Moreover, the participants with ASD were less accurate and made more omissions than the controls in the EM task. The implications of these findings for the establishment of tailored educational programs for children with high-functioning ASD are discussed. Full article

(This article belongs to the Special Issue Advances in Autism Spectrum Disorder: Etiopathogenesis, Clinical Phenotypes, Diagnosis and Treatment)

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16 pages, 998 KiB

Open AccessArticle

Subgroups of Children with Autism Spectrum Disorder without Intellectual Disability: A Longitudinal Examination of Executive and Socio-Adaptive Behaviors in Adolescence

by Rocio Rosello, Carmen Berenguer, Jose Martinez-Raga, Ana Miranda and Samuele Cortese

J. Clin. Med. 2021, 10(10), 2220; https://doi.org/10.3390/jcm10102220 - 20 May 2021

Cited by 5 | Viewed by 2864

Abstract

Within the autistic spectrum, there is remarkable variability in the etiology, presentation, and treatment response. This prospective study was designed to identify, through cluster analysis, subgroups of individuals with ASD without intellectual disability (ID) based on the severity of the core symptoms in [...] Read more.

Within the autistic spectrum, there is remarkable variability in the etiology, presentation, and treatment response. This prospective study was designed to identify, through cluster analysis, subgroups of individuals with ASD without intellectual disability (ID) based on the severity of the core symptoms in childhood. The secondary aim was to explore whether these subgroups and a group with typical development (TD) differ in cognitive, adaptive, and social aspects measured in adolescence. The sample at baseline was comprised of 52 children with ASD without ID and 37 children with TD, aged 7–11. Among the ASD group, three clusters were identified. Cluster 1 (40%), ‘high severity’, presented high symptom severity on the DSM-5 criteria and the Social Communication Questionnaire. Cluster 2 (34%) showed ‘moderate severity’ on most of the scores. Cluster 3 (25%) corresponded to ‘low severity’, showing moderate social impairment and low restrictive, repetitive patterns of behavior, interests and activities. At 5-year follow-up, 45 adolescents with ASD without ID and 27 adolescents with TD were assessed. All clusters had significantly more difficulties in EF, ToM, socialization and adaptive behavior compared to TD. Social and adaptive trajectories between the ASD subgroups were relatively different; Cluster 1 showed poorer socialization and daily living skills than the other two subgroups. These findings highlight the importance of fully assessing social, cognitive, and adaptive profiles to develop care plans tailored to specific needs. Full article

(This article belongs to the Special Issue Advances in Autism Spectrum Disorder: Etiopathogenesis, Clinical Phenotypes, Diagnosis and Treatment)

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26 pages, 1843 KiB

Open AccessArticle

Coaching via Telehealth: Caregiver-Mediated Interventions for Young Children on the Waitlist for an Autism Diagnosis Using Single-Case Design

by Megan G. Kunze, Wendy Machalicek, Qi Wei and Stephanie St. Joseph

J. Clin. Med. 2021, 10(8), 1654; https://doi.org/10.3390/jcm10081654 - 13 Apr 2021

Cited by 19 | Viewed by 4587

Abstract

Years can elapse between parental suspicion of a developmental delay and a diagnostic assessment, ultimately delaying access to medically necessary, autism-specific intervention. Using a single-case, concurrent multiple baseline design, autism spectrum disorder symptomology (i.e., higher-order restrictive and repetitive behaviors and interests; higher-order RRBIs) [...] Read more.

Years can elapse between parental suspicion of a developmental delay and a diagnostic assessment, ultimately delaying access to medically necessary, autism-specific intervention. Using a single-case, concurrent multiple baseline design, autism spectrum disorder symptomology (i.e., higher-order restrictive and repetitive behaviors and interests; higher-order RRBIs) was targeted in toddlers (21–35 months) waiting for a diagnostic appointment. Caregivers were coached via telehealth to mediate early intervention to decrease interfering, inflexible higher-order RRBIs during play using four evidence-based applied behavior analytic strategies: modeling, prompting, differential reinforcement of appropriate behaviors, and response interruption and redirection. Six mother–child dyads were recruited from pediatrician offices and early intervention service districts in the United States. All families were considered under-served, under-resourced, or living in rural locations. A visual analysis of the data combined with Tau-U revealed a strong basic effect between the intervention package and parent strategy use and child flexible and inflexible behavior. Findings were consistent across participants with one exception demonstrating a moderate effect for flexible behaviors yet a strong effect for inflexible behaviors. Standardized mean difference was beyond zero for all participants. Implications for science and practice include support for early intervention of higher-order RRBIs for young children with and at risk for ASD. Full article

(This article belongs to the Special Issue Advances in Autism Spectrum Disorder: Etiopathogenesis, Clinical Phenotypes, Diagnosis and Treatment)

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16 pages, 1567 KiB

Open AccessFeature PaperArticle

Autism Spectrum Disorder and Disruptive Behavior Disorders Comorbidities Delineate Clinical Phenotypes in Attention-Deficit Hyperactivity Disorder: Novel Insights from the Assessment of Psychopathological and Neuropsychological Profiles

by Gianluca Sesso, Chiara Cristofani, Stefano Berloffa, Paola Cristofani, Pamela Fantozzi, Emanuela Inguaggiato, Antonio Narzisi, Chiara Pfanner, Federica Ricci, Annalisa Tacchi, Elena Valente, Valentina Viglione, Annarita Milone and Gabriele Masi

J. Clin. Med. 2020, 9(12), 3839; https://doi.org/10.3390/jcm9123839 - 26 Nov 2020

Cited by 10 | Viewed by 2707

Abstract

Although childhood-onset psychiatric disorders are often considered as distinct and separate from each other, they frequently co-occur, with partial overlapping symptomatology. Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) commonly co-occur with each other and with other mental disorders, particularly disruptive behavior disorders, [...] Read more.

Although childhood-onset psychiatric disorders are often considered as distinct and separate from each other, they frequently co-occur, with partial overlapping symptomatology. Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) commonly co-occur with each other and with other mental disorders, particularly disruptive behavior disorders, oppositional defiant disorder/conduct disorder (ODD/CD). Whether these associated comorbidities represent a spectrum of distinct clinical phenotypes is matter of research. The aim of our study was to describe the clinical phenotypes of youths with ADHD with and without ASD and/or ODD/CD, based on neuropsychological and psychopathological variables. One-hundred fifty-one participants with ADHD were prospectively recruited and assigned to four clinical groups, and assessed by means of parent-reported questionnaires, the child behavior checklist and the behavior rating inventory of executive functions. The ADHD alone group presented a greater impairment in metacognitive executive functions, ADHD+ASD patients presented higher internalizing problems and deficits in Shifting tasks, and ADHD+ODD/CD subjects presented emotional-behavioral dysregulation. Moreover, ADHD+ASD+ODD/CD individuals exhibited greater internalizing and externalizing problems, and specific neuropsychological impairments in the domains of emotional regulation. Our study supports the need to implement the evaluation of the psychopathological and neuropsychological functioning profiles, and to characterize specific endophenotypes for a finely customized establishment of treatment strategies. Full article

(This article belongs to the Special Issue Advances in Autism Spectrum Disorder: Etiopathogenesis, Clinical Phenotypes, Diagnosis and Treatment)

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11 pages, 1394 KiB

Open AccessArticle

The Possibility of Intracranial Hypertension in Patients with Autism Spectrum Disorder Using Computed Tomography

by Shuichi Yamada, Ichiro Nakagawa, Fumihiko Nishimura, Yasushi Motoyama, Young-Soo Park and Hiroyuki Nakase

J. Clin. Med. 2020, 9(11), 3551; https://doi.org/10.3390/jcm9113551 - 04 Nov 2020

Cited by 1 | Viewed by 1692

Abstract

Although intracranial pressure is considered to be normal in children with autism spectrum disorder (ASD), we aimed to assess whether such children may have increased intracranial pressure using noninvasive computed tomography (CT). Head CT scans of children with ASD (109 cases, male 91 [...] Read more.

Although intracranial pressure is considered to be normal in children with autism spectrum disorder (ASD), we aimed to assess whether such children may have increased intracranial pressure using noninvasive computed tomography (CT). Head CT scans of children with ASD (109 cases, male 91 and female 18, average age 4.3 years) and of children with typical development (60 cases, male 35 and female 25, average age 4.5 years) were acquired. The images were processed to map the shape of the inner skull surface. We predicted that a complex skull shape, based on a marked digital impression, would be indicative of chronically increased intracranial pressure. The data of the scans were extracted and processed to automatically establish inner and outer cranial circumferences. The circularity (reflecting inner skull shape and area) and C-ratio (ratio of inner/outer circumference) were determined and statistically analyzed. The circularity and C-ratio were significantly lower in children with ASD than in children with typical development. A lower circularity was associated with a more complex shape of the inner skull surface, which indicated the presence of intracranial hypertension. Our study suggests that children with ASD may be at a risk for chronic intracranial hypertension. Our technique incorporating the circularity and C-ratio is a useful noninvasive method for screening such patients and could impact future investigations of ASD. Full article

(This article belongs to the Special Issue Advances in Autism Spectrum Disorder: Etiopathogenesis, Clinical Phenotypes, Diagnosis and Treatment)

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17 pages, 1230 KiB

Open AccessArticle

Methylphenidate in Autism Spectrum Disorder: A Long-Term Follow Up Naturalistic Study

by Patrizia Ventura, Concetta de Giambattista, Laura Spagnoletta, Paolo Trerotoli, Maddalena Cavone, Alessandra Di Gioia and Lucia Margari

J. Clin. Med. 2020, 9(8), 2566; https://doi.org/10.3390/jcm9082566 - 07 Aug 2020

Cited by 12 | Viewed by 3736

Abstract

Autism spectrum disorder (ASD) often co-occurs with attention deficit/hyperactivity disorder (ADHD). Although methylphenidate (MPH) efficacy and safety are well-demonstrated for ADHD, evidences are scant in the context of ASD. This naturalistic study aimed to analyze long-term MPH efficacy and safety in 40 ADHD [...] Read more.

Autism spectrum disorder (ASD) often co-occurs with attention deficit/hyperactivity disorder (ADHD). Although methylphenidate (MPH) efficacy and safety are well-demonstrated for ADHD, evidences are scant in the context of ASD. This naturalistic study aimed to analyze long-term MPH efficacy and safety in 40 ADHD children and adolescents with comorbid ASD, comparing them with 40 ones affected by ADHD without ASD. Treatment lasted from 6 to 156 months (longer than 24 months in more than three quarters of patients). Efficacy and safety were measured by clinical global impression and children global assessment scales; influence of intellectual functioning was examined. Comparisons between groups were made by Wilcoxon or Friedmann tests; relationships between functioning scores and other characteristics were analyzed by ordinal logistic and linear regression. Results demonstrated that MPH in patients with ASD was associated with significative reduction of illness severity, clinical improvement and amelioration of global functioning, without significant differences with patients having ADHD without ASD. The trend of reduction of illness severity and increase of global functioning were favorably related with intellectual functioning. No serious adverse events were reported. The findings showed that long-term MPH was effective and well-tolerated in ADHD children and adolescents with comorbid high functioning ASD. Full article

(This article belongs to the Special Issue Advances in Autism Spectrum Disorder: Etiopathogenesis, Clinical Phenotypes, Diagnosis and Treatment)

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Review

Jump to: Research, Other

17 pages, 836 KiB

Open AccessReview

Cranio-Facial Characteristics in Autism Spectrum Disorder: A Scoping Review

by Giuseppe Quatrosi, Dario Genovese, Giuseppe Galliano, Hugo Zoppé, Emanuele Amodio, Fréderique Bonnet-Brilhault and Gabriele Tripi

J. Clin. Med. 2024, 13(3), 729; https://doi.org/10.3390/jcm13030729 - 26 Jan 2024

Viewed by 1208

Abstract

Autism spectrum disorders (ASD) consist of a complex group of neurodevelopmental disorders characterised by qualitative impairments of social interactions, communication abilities, and a limited, stereotyped, and repetitive selection of interests and activities. In light of the imperative to identify a possible biomarker for [...] Read more.

Autism spectrum disorders (ASD) consist of a complex group of neurodevelopmental disorders characterised by qualitative impairments of social interactions, communication abilities, and a limited, stereotyped, and repetitive selection of interests and activities. In light of the imperative to identify a possible biomarker for ASD, it has been determined that craniofacial anomalies serve as significant risk factors for neurodevelopmental disorders. The aim of this scoping review is to deepen the knowledge of the scientific literature related to cranio-facial characteristics in individuals with ASD, with a particular focus on recent research advancements. The review was performed by employing the search strings ((“Autism Spectrum Disorder” OR autism OR ASD OR “Autism Spectrum”) AND (“facial morphology” OR “facial phenotype”)) on the databases PubMed/MEDLINE, Scopus, and ERIC as of March 9, 2023. The review comprised seven studies whose findings were obtained through quantitative analysis of Euclidean distances between anatomical landmarks. The examination of facial abnormalities represents a possible reliable diagnostic biomarker that could aid in the timely identification of ASD. Phenotypic characteristics that may serve as predictive indicators of the severity of autistic symptoms can be observed in certain individuals with ASD by applying anthropometric and instrumental measurements. The presence of a phenotype characterised by an increased intercanthal distance and a reduced facial midline height appears to be associated with a higher degree of severity in autistic symptoms. In addition, it is worth noting that facial asymmetry and facial masculinity can be considered reliable indicators for predicting a more severe manifestation of symptoms. Full article

(This article belongs to the Special Issue Advances in Autism Spectrum Disorder: Etiopathogenesis, Clinical Phenotypes, Diagnosis and Treatment)

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29 pages, 1355 KiB

Open AccessReview

Children with Autism Spectrum Disorder and Abnormalities of Clinical EEG: A Qualitative Review

by Chiara Bosetti, Luca Ferrini, Anna Rita Ferrari, Emanuele Bartolini and Sara Calderoni

J. Clin. Med. 2024, 13(1), 279; https://doi.org/10.3390/jcm13010279 - 03 Jan 2024

Viewed by 1617

Abstract

Over the last decade, the comorbidity between Autism Spectrum Disorder (ASD) and epilepsy has been widely demonstrated, and many hypotheses regarding the common neurobiological bases of these disorders have been put forward. A variable, but significant, prevalence of abnormalities on electroencephalogram (EEG) has [...] Read more.

Over the last decade, the comorbidity between Autism Spectrum Disorder (ASD) and epilepsy has been widely demonstrated, and many hypotheses regarding the common neurobiological bases of these disorders have been put forward. A variable, but significant, prevalence of abnormalities on electroencephalogram (EEG) has been documented in non-epileptic children with ASD; therefore, several scientific studies have recently tried to demonstrate the role of these abnormalities as a possible biomarker of altered neural connectivity in ASD individuals. This narrative review intends to summarize the main findings of the recent scientific literature regarding abnormalities detected with standard EEG in children/adolescents with idiopathic ASD. Research using three different databases (PubMed, Scopus and Google Scholar) was conducted, resulting in the selection of 10 original articles. Despite an important lack of studies on preschoolers and a deep heterogeneity in results, some authors speculated on a possible association between EEG abnormalities and ASD characteristics, in particular, the severity of symptoms. Although this correlation needs to be more strongly elucidated, these findings may encourage future studies aimed at demonstrating the role of electrical brain abnormalities as an early biomarker of neural circuit alterations in ASD, highlighting the potential diagnostic, prognostic and therapeutic value of EEG in this field. Full article

(This article belongs to the Special Issue Advances in Autism Spectrum Disorder: Etiopathogenesis, Clinical Phenotypes, Diagnosis and Treatment)

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13 pages, 584 KiB

Open AccessReview

Genotype–Phenotype Correlations in Relation to Newly Emerging Monogenic Forms of Autism Spectrum Disorder and Associated Neurodevelopmental Disorders: The Importance of Phenotype Reevaluation after Pangenomic Results

by Carla Lintas, Roberto Sacco, Alessia Azzarà, Ilaria Cassano and Fiorella Gurrieri

J. Clin. Med. 2021, 10(21), 5060; https://doi.org/10.3390/jcm10215060 - 29 Oct 2021

Cited by 4 | Viewed by 1862

Abstract

ASD genetic diagnosis has dramatically improved due to NGS technologies, and many new causative genes have been discovered. Consequently, new ASD phenotypes have emerged. An extensive exome sequencing study carried out by the Autism Sequencing Consortium (ASC) was published in February 2020. The [...] Read more.

ASD genetic diagnosis has dramatically improved due to NGS technologies, and many new causative genes have been discovered. Consequently, new ASD phenotypes have emerged. An extensive exome sequencing study carried out by the Autism Sequencing Consortium (ASC) was published in February 2020. The study identified 102 genes which are de novo mutated in subjects affected by autism spectrum disorder (ASD) or similar neurodevelopmental disorders (NDDs). The majority of these genes was already known to be implicated in ASD or NDDs, whereas approximately 30 genes were considered “novel” as either they were not previously associated with ASD/NDDs or very little information about them was present in the literature. The aim of this work is to review the current literature since the publication of the ASC paper to see if new data mainly concerning genotype–phenotype correlations of the novel genes have been added to the existing one. We found new important clinical and molecular data for 6 of the 30 novel genes. Though the broad and overlapping neurodevelopmental phenotypes observed in most monogenic forms of NDDs make it difficult for the clinical geneticist to address gene-specific tests, knowledge of these new data can at least help to prioritize and interpret results of pangenomic tests to some extent. Indeed, for some of the new emerging genes analyzed in the present work, specific clinical features emerged that may help the clinical geneticist to make the final diagnosis by associating the genetic test results with the phenotype. The importance of this relatively new approach known as “reverse phenotyping” will be discussed. Full article

(This article belongs to the Special Issue Advances in Autism Spectrum Disorder: Etiopathogenesis, Clinical Phenotypes, Diagnosis and Treatment)

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33 pages, 602 KiB

Open AccessReview

Subjective and Electroencephalographic Sleep Parameters in Children and Adolescents with Autism Spectrum Disorder: A Systematic Review

by Maria Giuseppina Petruzzelli, Emilia Matera, Donatella Giambersio, Lucia Marzulli, Alessandra Gabellone, Anna Rosi Legrottaglie, Anna Margari and Lucia Margari

J. Clin. Med. 2021, 10(17), 3893; https://doi.org/10.3390/jcm10173893 - 30 Aug 2021

Cited by 16 | Viewed by 2673

Abstract

Background: Sleep problems have commonly manifested in children and adolescents with autism spectrum disorder (ASD) with a complex and multifactorial interaction between clinical and etiological components. These disorders are associated with functional impairment, and provoke significant physical and mental affliction. The purpose of [...] Read more.

Background: Sleep problems have commonly manifested in children and adolescents with autism spectrum disorder (ASD) with a complex and multifactorial interaction between clinical and etiological components. These disorders are associated with functional impairment, and provoke significant physical and mental affliction. The purpose of this study is to update the existing literature about objective and subjective sleep parameters in children and adolescents with ASD, extrapolating information from polysomnography or sleep electroencephalography, and sleep related questionnaires. Methods: We have conducted a systematic review of case-control studies on this topic, performing a web-based search on PubMed, Scopus and the Web of Science databases according to the Preferred Reporting items for Systematic Review and Meta-analyses (PRISMA) guidelines. Results: Data collected from 20 survey result reports showed that children and adolescents with ASD experienced a higher rate of sleep abnormalities than in typically developing children. The macrostructural sleep parameters that were consistent with subjective parent reported measures unveil a greater percentage of nighttime signs of insomnia. Sleep microstructure patterns, in addition, pointed towards the bidirectional relationship between brain dysfunctions and sleep problems in children with ASD. Conclusions: Today’s literature acknowledges that objective and subjective sleep difficulties are more often recognized in individuals with ASD, so clinicians should assess sleep quality in the ASD clinical population, taking into consideration the potential implications on treatment strategies. It would be worthwhile in future studies to examine how factors, such as age, cognitive level or ASD severity could be related to ASD sleep abnormalities. Future research should directly assess whether sleep alterations could represent a specific marker for atypical brain development in ASD. Full article

(This article belongs to the Special Issue Advances in Autism Spectrum Disorder: Etiopathogenesis, Clinical Phenotypes, Diagnosis and Treatment)

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23 pages, 1073 KiB

Open AccessReview

Chromatin Remodeler CHD8 in Autism and Brain Development

by Anke Hoffmann and Dietmar Spengler

J. Clin. Med. 2021, 10(2), 366; https://doi.org/10.3390/jcm10020366 - 19 Jan 2021

Cited by 17 | Viewed by 4580

Abstract

Chromodomain Helicase DNA-binding 8 (CHD8) is a high confidence risk factor for autism spectrum disorders (ASDs) and the genetic cause of a distinct neurodevelopmental syndrome with the core symptoms of autism, macrocephaly, and facial dysmorphism. The role of CHD8 is well-characterized [...] Read more.

Chromodomain Helicase DNA-binding 8 (CHD8) is a high confidence risk factor for autism spectrum disorders (ASDs) and the genetic cause of a distinct neurodevelopmental syndrome with the core symptoms of autism, macrocephaly, and facial dysmorphism. The role of CHD8 is well-characterized at the structural, biochemical, and transcriptional level. By contrast, much less is understood regarding how mutations in CHD8 underpin altered brain function and mental disease. Studies on various model organisms have been proven critical to tackle this challenge. Here, we scrutinize recent advances in this field with a focus on phenotypes in transgenic animal models and highlight key findings on neurodevelopment, neuronal connectivity, neurotransmission, synaptic and homeostatic plasticity, and habituation. Against this backdrop, we further discuss how to improve future animal studies, both in terms of technical issues and with respect to the sex-specific effects of Chd8 mutations for neuronal and higher-systems level function. We also consider outstanding questions in the field including ‘humanized’ mice models, therapeutic interventions, and how the use of pluripotent stem cell-derived cerebral organoids might help to address differences in neurodevelopment trajectories between model organisms and humans. Full article

(This article belongs to the Special Issue Advances in Autism Spectrum Disorder: Etiopathogenesis, Clinical Phenotypes, Diagnosis and Treatment)

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15 pages, 1582 KiB

Open AccessReview

Gut-Induced Inflammation during Development May Compromise the Blood-Brain Barrier and Predispose to Autism Spectrum Disorder

by Rebecca S. Eshraghi, Camron Davies, Rahul Iyengar, Linda Perez, Rahul Mittal and Adrien A. Eshraghi

J. Clin. Med. 2021, 10(1), 27; https://doi.org/10.3390/jcm10010027 - 24 Dec 2020

Cited by 25 | Viewed by 8005

Abstract

Recently, the gut microbiome has gained considerable interest as one of the major contributors to the pathogenesis of multi-system inflammatory disorders. Several studies have suggested that the gut microbiota plays a role in modulating complex signaling pathways, predominantly via the bidirectional gut-brain-axis (GBA). [...] Read more.

Recently, the gut microbiome has gained considerable interest as one of the major contributors to the pathogenesis of multi-system inflammatory disorders. Several studies have suggested that the gut microbiota plays a role in modulating complex signaling pathways, predominantly via the bidirectional gut-brain-axis (GBA). Subsequent in vivo studies have demonstrated the direct role of altered gut microbes and metabolites in the progression of neurodevelopmental diseases. This review will discuss the most recent advancements in our understanding of the gut microbiome’s clinical significance in regulating blood-brain barrier (BBB) integrity, immunological function, and neurobiological development. In particular, we address the potentially causal role of GBA dysregulation in the pathophysiology of autism spectrum disorder (ASD) through compromising the BBB and immunological abnormalities. A thorough understanding of the complex signaling interactions between gut microbes, metabolites, neural development, immune mediators, and neurobiological functionality will facilitate the development of targeted therapeutic modalities to better understand, prevent, and treat ASD. Full article

(This article belongs to the Special Issue Advances in Autism Spectrum Disorder: Etiopathogenesis, Clinical Phenotypes, Diagnosis and Treatment)

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15 pages, 1213 KiB

Open AccessSystematic Review

Oral Health Statuses of Children and Young Adults with Autism Spectrum Disorder: An Umbrella Review

by Waqas Sami, Mohammad Shakil Ahmad, Riyaz Ahamed Shaik, Mohammad Miraj, Sadiya Ahmad and Muhammed Hamza Molla

J. Clin. Med. 2024, 13(1), 59; https://doi.org/10.3390/jcm13010059 - 22 Dec 2023

Cited by 1 | Viewed by 987

Abstract

This study aimed to comprehensively evaluate the oral health statuses of children and adults within the autism spectrum disorder (ASD) population through an umbrella review approach. The prevalence of dental caries, periodontal disease, and associated variables were investigated across selected studies. A systematic [...] Read more.

This study aimed to comprehensively evaluate the oral health statuses of children and adults within the autism spectrum disorder (ASD) population through an umbrella review approach. The prevalence of dental caries, periodontal disease, and associated variables were investigated across selected studies. A systematic search was conducted across databases including PubMed, Scopus, EMBASE, Science Citation Index, Science Direct, Web of Science, MEDLINE, and Wiley Online Library to identify relevant studies. The assessed variables included dental caries prevalence, periodontal disease prevalence, oral hygiene indicators, and the necessity of dental treatment. The pooled prevalence rates, odds ratios, and standardized mean differences were calculated where applicable. The pooled prevalence of dental caries among ASD individuals ranged from 60.6% to 67.3%, while the periodontal disease prevalence ranged from 59.8% to 69.4%. High rates of dental treatment under general anesthesia were reported. Heterogeneous dental caries and periodontal disease prevalence rates were identified, highlighting the need for collaboration and preventive care. Several studies also reported higher prevalence rates of dental trauma and self-inflicted oral injuries among individuals with ASD. However, the review also identified significant methodological limitations in the included studies, including inconsistency in oral health assessment methods and potential bias. The necessity for targeted policies due to high prevalence rates and the requirement for integrated care systems in high DMFT regions were also observed. The umbrella review synthesized diverse findings, revealing variations in dental caries and periodontal disease prevalence among ASD individuals. This review underscores the need for tailored interventions and policies to address oral health disparities. It highlights the necessity of integrated care systems, methodological improvements, and longitudinal studies to comprehensively address the multifaceted oral health challenges within the ASD population. Full article

(This article belongs to the Special Issue Advances in Autism Spectrum Disorder: Etiopathogenesis, Clinical Phenotypes, Diagnosis and Treatment)

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8 pages, 383 KiB

Open AccessCase Report

Autism Spectrum Disorder and Duchenne Muscular Dystrophy: A Clinical Case on the Potential Role of the Dystrophin in Autism Neurobiology

by Marta Simone, Lucia Margari, Francesco Pompamea, Andrea De Giacomo, Alessandra Gabellone, Lucia Marzulli and Roberto Palumbi

J. Clin. Med. 2021, 10(19), 4370; https://doi.org/10.3390/jcm10194370 - 24 Sep 2021

Cited by 3 | Viewed by 2424

Abstract

A diagnosis of autism spectrum disorder is reported in up to 19% of dystrophinopathies. However, over the last ten years, only a few papers have been published on this topic. Therefore, further studies are required to analyze this association in depth and ultimately [...] Read more.

A diagnosis of autism spectrum disorder is reported in up to 19% of dystrophinopathies. However, over the last ten years, only a few papers have been published on this topic. Therefore, further studies are required to analyze this association in depth and ultimately to understand the role of the brain dystrophin isoform in the pathogenesis of ASD and other neurodevelopmental disorders. In this paper, we report a clinical case of a patient affected by ASD and Duchenne muscular dystrophy, who carries a large deletion of the dystrophin gene. Then we present a brief overview of the literature about similar cases and about the potential role of the dystrophin protein in the neurobiology of autism spectrum disorder. Full article

(This article belongs to the Special Issue Advances in Autism Spectrum Disorder: Etiopathogenesis, Clinical Phenotypes, Diagnosis and Treatment)

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