Later onset of Childhood Disintegrative Disorder (CDD): a case report.

Childhood Disintegrative Disorder (CDD) is a rare condition characterized by regression of developmental and behavioral functioning after a period of apparently normal development, with an age of onset around 4 years. CDD is not included within the latest edition of the Diagnostic and Statistical Manual of Mental Disorders. We present a case report of an 11-year-old male who achieved normal development for up to 7 years followed by a deterioration of previously acquired linguistic, intellectual, and social skills. Following treatment with lithium carbonate combined with risperidone, the patient experienced a reduction in irritability and aggression. CDD is a rare condition; therefore, the data presented may be useful to investigate its characteristics of the onset, to improve the understanding of the aspects of differentiation from the Autism Spectrum Disorder and finally to propose the possibility of treatment.

Self-projection in middle childhood: a study on the relationship between theory of mind and episodic future thinking.

Growing evidence suggests that theory of mind (ToM) and episodic future thinking (EFT) are closely related at both brain and functional level. This study explored the relationship between ToM and EFT in 96 Italian-speaking children with typical development aged between 8 and 10.11 using a behavioral design. ToM was assessed through an emotional facial expression recognition task. EFT was assessed with a task where participants were required to project themselves forward in time by anticipating future states of the self; this resulted in two scores: a nonverbal measure and a verbal explanation measure. Results showed that the participants' performance on the task assessing ToM correlated with and predicted the nonverbal measure of the EFT task. These findings are discussed in the light of theories suggesting that each of these abilities is governed by a common system devoted to self-projection.

Cooperative parent-mediated therapy for Italian preschool children with autism spectrum disorder: a randomized controlled trial.

Parent-mediated intervention is widely used for pre-schoolers with autism spectrum disorder (ASD). Previous studies indicate small-to-moderate effects on social communication skills, but with a wide heterogeneity that requires further research. In this randomized controlled trial (RCT), cooperative parent-mediated therapy (CPMT) an individual parent coaching program for young children with ASD was administered to preschool children with ASD. All children received the same low-intensity psychosocial intervention (LPI) delivered in community settings, to evaluate the potential additional benefit of CPMT. Thirty-four participants with ASD (7 females; 27 males; aged 2, 6, 11 years) and their parents were included in the trial. The primary blinded outcome was social communication skills, assessed using the ADOS-G social communication algorithm score (ADOS-G SC). Secondary outcomes included ASD symptom severity, parent-rated language abilities and emotional/behavioral problems, and self-reported caregiver stress. Evaluations were made at baseline and post-treatment (at 6 months) by an independent multidisciplinary team. Results documented that CPMT showed an additional benefit on LPI with significant improvements of the primary blinded outcome, socio-communication skills, and of some secondary outcomes such as ASD symptom severity, emotional problems and parental stress related to parent-child dysfunctional interaction. No additional benefit was found for language abilities. Findings of our RCT show that CPMT provide an additional significant short-term treatment benefit on ASD core symptoms, when compared with active control group receiving only LPI.

Proteomics and Metabolomics Approaches towards a Functional Insight onto AUTISM Spectrum Disorders: Phenotype Stratification and Biomarker Discovery.

Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by behavioral alterations and currently affect about 1% of children. Significant genetic factors and mechanisms underline the causation of ASD. Indeed, many affected individuals are diagnosed with chromosomal abnormalities, submicroscopic deletions or duplications, single-gene disorders or variants. However, a range of metabolic abnormalities has been highlighted in many patients, by identifying biofluid metabolome and proteome profiles potentially usable as ASD biomarkers. Indeed, next-generation sequencing and other omics platforms, including proteomics and metabolomics, have uncovered early age disease biomarkers which may lead to novel diagnostic tools and treatment targets that may vary from patient to patient depending on the specific genomic and other omics findings. The progressive identification of new proteins and metabolites acting as biomarker candidates, combined with patient genetic and clinical data and environmental factors, including microbiota, would bring us towards advanced clinical decision support systems (CDSSs) assisted by machine learning models for advanced ASD-personalized medicine. Herein, we will discuss novel computational solutions to evaluate new proteome and metabolome ASD biomarker candidates, in terms of their recurrence in the reviewed literature and laboratory medicine feasibility. Moreover, the way to exploit CDSS, performed by artificial intelligence, is presented as an effective tool to integrate omics data to electronic health/medical records (EHR/EMR), hopefully acting as added value in the near future for the clinical management of ASD.

An investigation of visual narrative comprehension in children with autism spectrum disorders.

The present study analyzed the comprehension of visual narrative in a group of twelve children with autism spectrum disorders (ASD). Their performances were compared to a control group of fifteen children with typical development (TD) matched for age, level of formal education, and IQ. Visual narrative comprehension was assessed by administering a task that required children to understand narrative's global coherence by arranging in the correct order the constituent parts of stories presented in pictures. Specifically, the task evaluated children's ability to grasp how single events connected (causally and temporally) each other and how these connections led to the ending of the story. Results showed that children with ASD obtained significantly lower scores than children with TD. These results open to alternative interpretations of narrative impairments often reported in individuals with ASD, which might not be restricted to the linguistic code but stem from a deeper deficit in narrative processing that is independent from the expressive modality.

Behavioral phenotype in Costello syndrome with atypical mutation: a case report.

Costello syndrome (CS) is a rare genetic disorder caused, in the majority of cases, by germline missense HRAS mutations affecting Gly(12) promoting enhanced signaling through the MAPK and PI3K-AKT signaling cascades. In general, the cognitive profile in CS is characterized by intellectual disability ranging from mild to severe impairment. The first published descriptions of behavior in CS children underlined the presence of irritability and shyness at younger ages with sociable personality and good empathic skills after 4-5 years of age, however some recent studies have reported autistic traits. We report on a 7-year-old boy heterozygous for a rare duplication of codon 37 (p.E37dup) in HRAS, manifesting impaired social interaction and non-verbal communication and with circumscribed interests. These additional features improve phenotype delineation in individuals with rare HRAS mutations, facilitating the development of specific behavioral treatments which could lead to improvement in cases of autism spectrum disorder.

Association between child behavioural problems and parenting stress in autism spectrum disorders: the role of parenting self-efficacy.

Introduction: The present study build on previous research that found a bidirectional relation of parenting stress and negative behavioural outcomes in children with Autism Spectrum Disorders. Aim: To investigate the mediating role of parenting self-efficacy in the relationship of parenting stress and children's behavioural and emotional problems. Materials and methods: The sample included 32 young children and their families. Sociodemographic and clinical data were collected. Hierarchical regression analysis revealed direct and indirect mediating effects. Results: Parenting self-efficacy mediated the relationship between parenting stress and children's behavioural and emotional problems in fathers only. Conclusions: We discuss potential ways targeted parenting self-efficacy intervention can support fathers. Results contribute to gain father-informed knowledge in, a research branch generally focused on mothers.

Correction of Batch Effect in Gut Microbiota Profiling of ASD Cohorts from Different Geographical Origins.

BACKGROUND: To date, there have been numerous metataxonomic studies on gut microbiota (GM) profiling based on the analyses of data from public repositories. However, differences in study population and wet and dry pipelines have produced discordant results. Herein, we propose a biostatistical approach to remove these batch effects for the GM characterization in the case of autism spectrum disorders (ASDs). METHODS: An original dataset of GM profiles from patients with ASD was ecologically characterized and compared with GM public digital profiles of age-matched neurotypical controls (NCs). Also, GM data from seven case-control studies on ASD were retrieved from the NCBI platform and exploited for analysis. Hence, on each dataset, conditional quantile regression (CQR) was performed to reduce the batch effects originating from both technical and geographical confounders affecting the GM-related data. This method was further applied to the whole dataset matrix, obtained by merging all datasets. The ASD GM markers were identified by the random forest (RF) model. RESULTS: We observed a different GM profile in patients with ASD compared with NC subjects. Moreover, a significant reduction of technical- and geographical-dependent batch effects in all datasets was achieved. We identified Bacteroides_H, Faecalibacterium, Gemmiger_A_73129, Blautia_A_141781, Bifidobacterium_388775, and Phocaeicola_A_858004 as robust GM bacterial biomarkers of ASD. Finally, our validation approach provided evidence of the validity of the QCR method, showing high values of accuracy, specificity, sensitivity, and AUC-ROC. CONCLUSIONS: Herein, we proposed an updated biostatistical approach to reduce the technical and geographical batch effects that may negatively affect the description of bacterial composition in microbiota studies.

"BottegaMente": An Italian program of internship for people with autism spectrum disorder.

BACKGROUND: Transitioning into adulthood can be challenging for individuals with Autism Spectrum Disorder (ASD). Work is one of the most enduring and impactful aspects of adult life, as it plays a key role in helping people find meaning. However, research on the effectiveness of pre-employment programs in improving the health and well-being of autistic adolescents and young adults remains limited. This exploratory study aims to assess the impact of a nationwide internship program, "BottegaMente", on the adaptive functioning, emotion regulation, and quality of life of autistic teens, adults, and their families. METHOD: The program involved 82 participants, aged 13-36, and required active family involvement to ensure it addressed the needs of autistic individuals from the planning stages through implementation. Quantitative data were collected before (T0) and after the internship (T1). RESULTS: Our study demonstrated that the internship effectively enhanced adaptive skills, particularly in areas like home life and work skills for autistic adolescents and adults, as reflected by standardized outcomes at T1 compared to T0. CONCLUSION: This research is one of the pioneering efforts to evaluate the effectiveness of pre-employment internship programs for autistic adolescents and adults. Although preliminary, these findings could help to shape future studies on employment, an essential factor for overall quality of life and well-being.

Treatment of Aggressive Behavior and Agitation in an 11-Year-Old Boy with Co-Occurring Autism and ADHD: A Case Report and Literature Review on the Use of Intravenous Valproate in Emergency Psychiatry.

Background: Autism spectrum disorder (ASD) is a persistent neurodevelopmental disorder frequently co-occurring with attention-deficit/hyperactivity disorder (ADHD) and behavior-related disorders. While behavioral therapy is the first-line option to manage the core symptoms of ASD, pharmacological therapy is sometimes needed to treat acute problems, such as agitation and aggressive behaviors. Recent guidelines recommend the use of neuroleptics to reduce psychomotor agitation in patients with ASD. However, as children with ASD are often drug-resistant, alternative treatments are often justified. Reports from the literature have indicated that intravenous valproate (IV-VPA) can be effective in reducing agitation in psychiatric patients, with a lower frequency of adverse events compared to conventional treatments. However, as the related findings are occasionally inconsistent, IV-VPA is not yet an approved option in the context of clinical psychiatry. We aim to improve knowledge of the IV-VPA treatment option for emergency psychiatric treatment in pediatric patients. Methods: We report the case of an 11-year-old boy suffering from a complex neurodevelopmental condition who experienced a psychotic episode with severe aggressive and disruptive behaviors and was successfully treated with IV-VPA. Furthermore, we provide an updated literature review on this topic. Conclusion: In our case, first-line therapies proved to be ineffective. To the contrary, IV-VPA led to safe and prompt clinical success, which is in line with other reports. Based on our literature review, IV-VPA can be highly effective and reduces the risk of adverse events that frequently occur with the use of high-dose standard medications in emergency psychiatry.

Stratification of Gut Microbiota Profiling Based on Autism Neuropsychological Assessments.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder. Investigations of gut microbiota (GM) play an important role in deciphering disease severity and symptoms. Overall, we stratified 70 ASD patients by neuropsychological assessment, based on Calibrated Severity Scores (CSSs) of the Autism Diagnostic Observation Schedule-Second edition (ADOS-2), Child Behavior Checklist (CBCL) and intelligent quotient/developmental quotient (IQ/DQ) parameters. Hence, metataxonomy and PICRUSt-based KEGG predictions of fecal GM were assessed for each clinical subset. Here, 60% of ASD patients showed mild to moderate autism, while the remaining 40% showed severe symptoms; 23% showed no clinical symptoms, 21% had a risk of behavior problems and 56% had clinical symptoms based on the CBCL, which assesses internalizing problems; further, 52% had no clinical symptoms, 21% showed risk, and 26% had clinical symptoms classified by CBCL externalizing problems. Considering the total CBCL index, 34% showed no clinical symptoms, 13% showed risk, and 52% had clinical symptoms. Here, 70% of ASD patients showed cognitive impairment/developmental delay (CI/DD). The GM of ASDs with severe autism was characterized by an increase in Veillonella, a decrease in Monoglobus pectinilyticus and a higher microbial dysbiosis index (MDI) when compared to mild-moderate ASDs. Patients at risk for behavior problems and showing clinical symptoms were characterized by a GM with an increase of Clostridium, Eggerthella, Blautia, Intestinibacter, Coprococcus, Ruminococcus, Onthenecus and Bariatricus, respectively. Peptidoglycan biosynthesis and biofilm formation KEGGs characterized patients with clinical symptoms, while potential microbiota-activated PPAR-γ-signaling was seen in CI/DD patients. This evidence derived from GM profiling may be used to further improve ASD understanding, leasing to a better comprehension of the neurological phenotype.

Sleep Disturbances and Co-sleeping in Italian Children and Adolescents with Autism Spectrum Disorder.

The current study aimed (1) to provide an analysis of the frequency and prevalence of sleep disturbances in a large Italian sample of children and adolescents with ASD, detecting specific predictors of the presence/absence of sleep disorders, (2) to examine the phenomenon of co-sleeping within a subgroup of participants with ASD. A total of 242 children and adolescents with ASD (194 males, mean age 5.03 ± 3.15 years) were included. After the diagnostic procedure, caregivers were requested to complete the Sleep Disturbance Scale for Children (SDSC) to assess sleep disorders among participants. The presence of co-sleeping was investigated in a subgroup of 146 children and adolescents with ASD. An elevated or clinically relevant global score for sleep disorders (≥ 60) was found in 33% of participants. The most prevalent sleep disorder in our group was related to difficulties with sleep onset and sleep maintenance (~ 41% of cases). Sleep disturbances were predicted by higher intelligence quotient (IQ)/developmental quotient (DQ), increased internalizing problems, and elevated parental stress. The subgroup of participants engaged in co-sleeping (N = 87) were younger and had lower IQ/DQ scores, reduced adaptive functioning, and diminished psychological wellbeing than the non-co-sleeping group. Our findings are consistent with the current literature highlighting that insomnia is the most widespread sleep problem associated with ASD. The relationship between IQ/DQ and sleep alterations is a crucial topic that deserves additional research. Future studies should assess sleep by objective measures such as EEG topography to better understand the mechanisms underlying sleep alterations in this neurodevelopmental disorder.

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

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.

Autism Spectrum Disorder and Early Psychosis: a narrative review from a neurodevelopmental perspective.

Autism Spectrum Disorder (ASD), characterized by socio-communicative abnormalities and restricted, repetitive, and stereotyped behaviors, is part of Neurodevelopmental Disorders (NDDs), a diagnostic category distinctly in accordance with the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, (DSM-5), clearly separated from Schizophrenia Spectrum Disorder (SSD) (schizophrenia, schizophreniform disorder, schizoaffective disorder, schizotypal personality disorder). Over the last four decades, this clear distinction is gradually being replaced, describing ASD and SSD as two heterogeneous conditions but with neurodevelopmental origins and overlaps. Referring to the proposal of a neurodevelopmental continuum model, the current research's aim is to provide an update of the knowledge to date on the course of clinical symptoms and their overlaps among ASD and SSD. A narrative review of the literature published between January 2010 and June 2023 was conducted. Five studies were included. All studies show a global impairment in both conditions. Two studies show a focus on neurodevelopmental perspective in ASD and SSD. Only one study of these adopts a longitudinal prospective in terms of prognostic markers among ASD and SSD. Three studies underline the overlap between ASD and SSD in terms of negative, disorganized and positive symptomatology. To date, there is a gap in the current scientific literature focused on ASD-SSD course of clinical symptoms and their overlaps from a neurodevelopmental perspective. Future longitudinal studies to identify risk markers and tailored treatments are needed.

Deaf children attending different school environments: sign language abilities and theory of mind.

The present study examined whether full access to sign language as a medium for instruction could influence performance in Theory of Mind (ToM) tasks. Three groups of Italian participants (age range: 6-14 years) participated in the study: Two groups of deaf signing children and one group of hearing-speaking children. The two groups of deaf children differed only in their school environment: One group attended a school with a teaching assistant (TA; Sign Language is offered only by the TA to a single deaf child), and the other group attended a bilingual program (Italian Sign Language and Italian). Linguistic abilities and understanding of false belief were assessed using similar materials and procedures in spoken Italian with hearing children and in Italian Sign Language with deaf children. Deaf children attending the bilingual school performed significantly better than deaf children attending school with the TA in tasks assessing lexical comprehension and ToM, whereas the performance of hearing children was in between that of the two deaf groups. As for lexical production, deaf children attending the bilingual school performed significantly better than the two other groups. No significant differences were found between early and late signers or between children with deaf and hearing parents.

Early and stable difficulties of everyday executive functions predict autism symptoms and emotional/behavioral problems in preschool age children with autism: a 2-year longitudinal study.

Introduction: Longitudinal studies of autistic children show that autism symptoms and emotional/behavioral problems vary and change over time. However, the factors that affect this variability remain far from certain and very little is known about what take place in the preschool period and the role of executive functions (EF). Methods: Here, we test the influence of stable difficulties in everyday executive functioning (EEF) during early childhood across 2 years on autistic symptoms and emotional and behavioral problems. Twenty-nine autistic children (24 males and 5 females) were assessed twice within the space of 2 years. At baseline (M = 29 months, SD =5.6 months), participants were assessed for EEF, cognitive development, autistic symptoms, and emotional/behavioral problems. At follow-up, we repeated the same assessment except for cognitive development. Results: The group with stable difficulties (across 2 years) in EEF during early childhood showed a worsening in the severity of autistic symptoms and emotional and behavioral problems compared with children without EEF difficulties (p < 0.05), and these effects cannot be attributable to cognitive development. Discussion: Our results suggest that early and stable EEF plays the role of a modifier by interacting with the core domains of autism, in particular with the social affect domain (SA CSS), influencing social cognition and exacerbating or lessening symptom expression and emotional behavioral problems. These short-term longitudinal and preliminary findings underscore the importance of EEF as necessary target for early intervention in children with autism.

Psychiatric Comorbidities in Children and Adolescents with High-Functioning Autism Spectrum Disorder: A Study on Prevalence, Distribution and Clinical Features in an Italian Sample.

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.

Autism spectrum disorder, very-early onset schizophrenia, and child disintegrative disorder: the challenge of diagnosis. A case-report study.

Background: Autism spectrum disorder (ASD) in the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) contains several disorders previously present as distinct diagnoses in the DSM Revised Fourth Edition (DSM-IV-TR). These include child disintegrative disorder (CDD). The latter presents typical features, such as a late regression of developmental acquisitions. However, it also shows symptoms similar to ASD, and psychotic symptoms, such as very-early onset schizophrenia (VEOS), are described in the literature. Case report: In this case report we deepen the case of P., a child who presents a late regression, at 7 years old, associated with psychotic symptoms in the absence of organic alterations. The child was treated with antipsychotic drug therapy and cognitive behavioral therapy. P. was diagnosed with ASD with acute and late regression associated with psychotic symptoms. During the follow-up, there was a gradual improvement in the clinical conditions. Improvements were possible due to therapeutic intervention (pharmacological and psychotherapeutic) and/or the natural course of the disorder. Conclusion: The diagnostic difficulty of this case reflects a clinical complexity in which it is not easy to distinguish between neurodevelopmental and psychiatric aspects. Clinical cases such as that of P. emphasize the theme of the neurodevelopment continuum model in which neurodevelopmental and psychiatric disturbances can be considered within a pattern of pathological continuity.

Defining the Characteristics of Story Production of Autistic Children: A Multilevel Analysis.

Several studies suggest that a valuable tool to examine linguistic skills in communication disorders is offered by procedures of narrative discourse assessment. Following this line of research, we present an exploratory study aimed to investigate storytelling abilities of autistic children to better define the characteristics of their story production. Participants included 41 autistic children and 41 children with typical development aged between 7.02 and 11.03 years matched on age, gender, level of formal education, intelligence quotient, working memory, attention skills, theory of mind, and phonological short-term memory. Narrative production was assessed by analysing the language samples obtained through the "Nest Story" description task. A multilevel analysis including micro- and macro-linguistic variables was adopted for narrative assessment. Group differences emerged on both micro- and macro-linguistic dimensions: autistic children produced narratives with more phonological errors and semantic paraphasias (microlinguistic variables) as well as more errors of global coherence and a fewer number of visible events and inferred events (macrolinguistic variables) than the control group.This study shows that even autistic children with adequate cognitive skills display several limitations in their narrative competence and that such weaknesses affect both micro- and macrolinguistic aspects of story production.

The teleNIDA: Early Screening of Autism Spectrum Disorder Through a Novel Telehealth Approach.

The COVID-19 pandemic has fast-tracked interest in telehealth methods to guarantee the continuity of care of children with Autism Spectrum Disorder (ASD). Store-and-forward telehealth approaches offer the opportunity to facilitate timely screening of ASD, allowing parents to record videos of their child's behaviors, subsequently shared with clinicians that provide an assessment remotely. This study aimed to examine the psychometric properties of a new telehealth screening tool, the teleNIDA, administered in home settings for remote observation of early signs of ASD in toddlers aged 18-30 months. Results showed good psychometric properties of the teleNIDA, as compared to the gold standard in-person assessment, and the predictive validity on the diagnosis of ASD at 36 months was demonstrated. This study supports the teleNIDA as a promising level 2 screening tool for ASD able to speed up diagnostic and intervention processes.