Clozapine Treatment for Aggressive Behaviors in Youths with Neurodevelopmental Disorders.

Objectives: The aim of this study was to assess effectiveness and tolerability of Clozapine in the treatment of aggression in youth with Neurodevelopmental Disorders. Methods: Patients were consecutively admitted at our third-level university hospital with nationwide catchment from June 2018 to October 2022, and followed up to July 2023. Eligibility criteria were as follows: (1) Autism Spectrum Disorder (ASD) and/or Intellectual Disability/Borderline Cognitive Functioning, (2) behavioral dyscontrol with physical aggression; (3) age range between 8 and 18 years; (4) clinical indication for Clozapine treatment after at least two failed trials with other Second-Generation Antipsychotics (SGAs); (5) availability of an at least 6-month-long follow-up. To evaluate the response to Clozapine, we used the Clinical Global Impressions (CGI) rating scales (Clinical Global Impressions-Severity [CGI-S] and Clinical Global Impressions-Improvement [CGI-I]), the Children's Global Assessment Scale (CGAS), and the Aberrant Behavior Checklist (ABC). Results: Twenty-six children and adolescents (21 boys, age 13.47 ± 2.05 years, follow-up duration 9.77 ± 3.50 months) were included in the analysis. Clinical severity (CGI-S) and functional impairment (Clinical Global Assessment Scale) significantly improved, as well as the ABC Total Score and the scores in several subscales. Sixteen patients (61.54%) were responders (CGI-I ≤2), and 13 (50.00%) displayed remission of aberrant behaviors (ΔABC-Total >35), while response/remission condition was not affected by add-on medications and psychotherapy. Most frequent side effects were increased appetite (50.00%), sialorrhea (38.46%), and increased repetitive behaviors (26.92%). Two patients presented epileptic seizures, while no patients presented leucopoenia. Conclusions: Our results suggest that Clozapine may be helpful in ameliorating treatment-resistant aggression in youth with neurodevelopmental conditions. Possible pharmacological strategies for the management of most frequent side effects are also suggested.

Internet Gaming Disorder in Children and Adolescents with Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder.

Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) have been related to an increased risk for behavioral addictions including online gaming. However, the relationship between these two conditions and Internet gaming disorder (IGD) is still debated. The aim of this study is to address this topic by exploring the prevalence of IGD in a consecutive sample of ASD youth and ADHD youth, compared with a normal control group, and by assessing selected psychopathological and neuropsychological features in ASD and ADHD patients with and without IGD. This study included 77 ASD patients (67 males, mean age 13.58 ± 2.75 years), 94 ADHD patients (79 males, mean age 11.46 ± 2.47 years), and 147 normal controls (NC) (mean age 13.9 ± 3.0 years, 114 males) that received structured measures for IGD (IAT, IGDS9-SF, and UADI). In the ADHD group, 72.34% of the sample were above the IGD cut-off, compared with 45.45% in the ASD group and 9.5% in the NC group. ASD patients with IGD presented with greater severity and more severe attention problems, with no difference in the ASD core symptoms between patients with and without IGD. In the comparison between the ASD and ADHD groups according to the presence of IGD, ASD patients with IGD were the most severe group according to the CGI (Clinical Global Impression) scale. The follow-up, conducted on 45 patients affected by ASD, showed an improvement in CGI and CGAS (Children's Global Assessment Scale) scores, but not in the IGD symptoms. These findings could place the diagnosis of ASD as a negative prognostic factor in the follow-up of aspects of video game addiction compared with ADHD.

The Developmental Autism Early Screening (DAES): A Novel Test for Screening Autism Spectrum Disorder.

This study was undertaken to set a novel developmental screening test for autism spectrum disorder (ASD) using the Griffiths Scales of Child Development (Griffith III) (Green et al., 2016; Stroud et al., 2016), in order to intercept the early atypical developmental patterns indicating ASD risk in the first 3 years of age. An observational and interactive ASD screener, the Developmental Autism Early Screening (DAES), was developed by detecting Griffiths III items differentiating toddlers with ASD risk from those with global developmental delay (DD) or neurotypical development. The DAES was validated with ASD-specific diagnostic instruments (ADOS-2) and the cut-off score based on sensitivity, specificity and positive predictive value that best differentiates between ASD and non-ASD children was identified. We enrolled a total sample of 297 subjects, including children at risk for ASD or DD and neurotypical children. At a cut-off score of 12.5, the DAES had a sensitivity of 93%, specificity of 98.4%, positive predictive value of 96.3% and negative predictive value of 96.9% for identifying children at risk for ASD from non-ASD participants (DD/neurotypical children). The DAES total score correlated significantly with the ADOS-2 calibrated severity scores (CSS) (R = 0.53, p < 0.001). Three ASD risk ranges were identified according to DAES total and ADOS-2 CSS: Little-to-no risk (CSS: 1-3, DAES: 1-7); Mild-to-moderate risk (CSS: 4-5, DAES: 8-14); Moderate-to-severe risk (CSS: 6-10, DAES ≥ 15). The DAES provides a direct approach based on developmental profiles to stratify risk for ASD in early childhood ensuring at risk children the most appropriate diagnostic procedures and targeted intervention.

Hikikomori (Severe Social Withdrawal) in Italian Adolescents: Clinical Features and Follow-Up.

Severe social withdrawal, including staying alone in one's bedroom, non-attendance at school or work, and minimal or absent social contacts, sometimes only through electronic devices, can be found in several psychiatric disorders, or in a 'primary' form, firstly defined in Japan as 'Hikikomori'. The distinction between primary and secondary forms is questionable, as it prevalently depends on the quality of psychiatric assessment. To date, few studies specifically explored Hikikomori in an adolescent population outside Japan. The aim of the present study is to describe clinical features of a consecutive group of 80 referred youth (13 to 18 years, 57 males) with social isolation, of which 40 were followed up on for 4-6 months, to characterize clinical features and outcome. All the participants presented psychiatric comorbid disorders, prevalently anxiety disorders, mood disorders, and autism spectrum disorder. Suicidality (ideation and behavior) was reported in 32.5% of the participants, and 20% of the participants attempted suicide. More than half of the participants exceeded the cut-off of the Internet Addiction Test, and 42.4% met the criteria for the Internet Gaming Disorder. At the follow-up appointment, an improvement of social withdrawal was reported in 75% of the sample; 67.5% of the participants significantly improved according to the CGI-improvement scale; and 55% of the participants had an improvement of functioning according to the C-GAS. Our findings suggest that Hikikomori is a transnosographic entity, with high rates of suicidality and Internet addiction, and that can it improve when it is timely diagnosed and treated.

Sex/Gender Differences in the Language Profiles of Italian Children with Autism Spectrum Disorder: A Retrospective Study.

Sex/gender (S/G) differences in ASD language profiles have been poorly investigated. The present study aims to explore whether male (M) and female (F) children with ASD and with normal non-verbal cognitive abilities differ in their linguistic profiles. A sample of 76 Italian children with ASD (range: 4.9-8 years), including 50 Ms and 26 Fs, was retrospectively recruited. Language profiles were analyzed using standardized tests for the evaluation of receptive and expressive vocabulary as well as grammar. Grammatical comprehension was the most impaired domain compared to the other language measures in both M and F children. Comparing language profiles between S/G, Fs showed significantly better scores than Ms in grammatical production (p = 0.002), and Ms showed better active negative sentence comprehension (p = 0.035). Moreover, comparing the language profiles between Ms and Fs with a receptive disorder, Fs had significantly worse grammatical comprehension and better grammatical production than Ms. Even among children without a receptive disorder, Fs had significantly higher grammatical production scores. The S/G differences in language profile, particularly better expressive language in Fs than Ms, can partially contribute to the delayed ASD diagnosis or underdiagnosis of Fs without intellectual disability. Finally, the results document the importance of accurately investigating both expressive and receptive abilities in children with ASD.

Persistent Non-Suicidal Self-Injury and Suicidality in Referred Adolescents: A Longitudinal Study Exploring the Role of Cyclothymic Temperament.

Non-suicidal self-injury (NSSI) is deliberate harm to the body surface without suicidal intent, though it may be a predictor of suicide attempts. Our aim was to test the hypothesis that persisting and recovering NSSI may have a different longitudinal risk for suicidal ideation and behavior and that the intensity of Cyclothymic Hypersensitive Temperament (CHT) may increase this risk. Fifty-five patients (mean age 14.64 ± 1.77 years) referred for mood disorders according to the DSM-5 were consecutively recruited and followed-up for a mean of 19.79 ± 11.67 months and grouped according to the presence/absence of NSSI at baseline and follow-up into three groups: without NSSI (non-NSSI; n = 22), with NSSI recovered at follow-up (past-NSSI; n = 19), and with persistent NSSI at follow-up (pers-NSSI; n = 14). At follow-up, both NSSI groups were more severely impaired and failed to improve internalizing problems and dysregulation symptoms. Both NSSI groups reported higher scores in suicidal ideation compared to non-NSSI, but only pers-NSSI presented higher scores in suicidal behavior. CHT was higher in pers-NSSI, followed by past-NSSI and then by non-NSSI. Our data support a continuity between NSSI and suicidality, and they suggest the prognostic validity of persistent NSSI, associated with highest CHT scores.

Autism and Children: Diagnosis, Functional Profiles and Intervention.

In the last forty years, approaches to and the social perception of autism have changed significantly [...].

Autism and Neurodevelopmental Disorders: The SARS-CoV-2 Pandemic Implications.

The Special Issue (SI) "Autism and Neurodevelopmental Disorders: The SARS-CoV-2 Pandemic Implications" is an interesting project that adopted a scientific point of view with important implications in clinical and practical fields [...].

Advances in Autism Research: Series II.

"Advances in Autism Research: Series II" is a continuation of the important Special Issue (SI) published in 2020 that collected 50 articles [...].

CRISIS AFAR: an international collaborative study of the impact of the COVID-19 pandemic on mental health and service access in youth with autism and neurodevelopmental conditions.

BACKGROUND: Heterogeneous mental health outcomes during the COVID-19 pandemic are documented in the general population. Such heterogeneity has not been systematically assessed in youth with autism spectrum disorder (ASD) and related neurodevelopmental disorders (NDD). To identify distinct patterns of the pandemic impact and their predictors in ASD/NDD youth, we focused on pandemic-related changes in symptoms and access to services. METHODS: Using a naturalistic observational design, we assessed parent responses on the Coronavirus Health and Impact Survey Initiative (CRISIS) Adapted For Autism and Related neurodevelopmental conditions (AFAR). Cross-sectional AFAR data were aggregated across 14 European and North American sites yielding a clinically well-characterized sample of N = 1275 individuals with ASD/NDD (age = 11.0 ± 3.6 years; n females = 277). To identify subgroups with differential outcomes, we applied hierarchical clustering across eleven variables measuring changes in symptoms and access to services. Then, random forest classification assessed the importance of socio-demographics, pre-pandemic service rates, clinical severity of ASD-associated symptoms, and COVID-19 pandemic experiences/environments in predicting the outcome subgroups. RESULTS: Clustering revealed four subgroups. One subgroup-broad symptom worsening only (20%)-included youth with worsening across a range of symptoms but with service disruptions similar to the average of the aggregate sample. The other three subgroups were, relatively, clinically stable but differed in service access: primarily modified services (23%), primarily lost services (6%), and average services/symptom changes (53%). Distinct combinations of a set of pre-pandemic services, pandemic environment (e.g., COVID-19 new cases, restrictions), experiences (e.g., COVID-19 Worries), and age predicted each outcome subgroup. LIMITATIONS: Notable limitations of the study are its cross-sectional nature and focus on the first six months of the pandemic. CONCLUSIONS: Concomitantly assessing variation in changes of symptoms and service access during the first phase of the pandemic revealed differential outcome profiles in ASD/NDD youth. Subgroups were characterized by distinct prediction patterns across a set of pre- and pandemic-related experiences/contexts. Results may inform recovery efforts and preparedness in future crises; they also underscore the critical value of international data-sharing and collaborations to address the needs of those most vulnerable in times of crisis.

High-Risk Siblings without Autism: Insights from a Clinical and Eye-Tracking Study.

Joint attention (JA)-the human ability to coordinate our attention with that of other people-is impaired in the early stage of Autism Spectrum Disorder (ASD). However, little is known about the JA skills in the younger siblings of children with ASD who do not develop ASD at 36 months of age [high-risk (HR)-noASD]. In order to advance our understanding of this topic, a prospective multicenter observational study was conducted with three groups of toddlers (age range: 18-33 months): 17 with ASD, 19 with HR-noASD and 16 with typical development (TD). All subjects underwent a comprehensive clinical assessment and an eye-tracking experiment with pre-recorded stimuli in which the visual patterns during two tasks eliciting initiating joint attention (IJA) were measured. Specifically, fixations, transitions and alternating gaze were analyzed. Clinical evaluation revealed that HR-noASD subjects had lower non-verbal cognitive skills than TD children, while similar levels of restricted and repetitive behaviors and better social communication skills were detected in comparison with ASD children. Eye-tracking paradigms indicated that HR-noASD toddlers had visual patterns resembling TD in terms of target-object-to-face gaze alternations, while their looking behaviors were similar to ASD toddlers regarding not-target-object-to-face gaze alternations. This study indicated that high-risk, unaffected siblings displayed a shared profile of IJA-eye-tracking measures with both ASD patients and TD controls, providing new insights into the characterization of social attention in this group of toddlers.

Reading Behaviors through Patterns of Finger-Tracking in Italian Children with Autism Spectrum Disorder.

The paper proposes an ecological and portable protocol for the large-scale collection of reading data in high-functioning autism spectrum disorder (ASD) children based on recording the finger movements of a subject reading a text displayed on a tablet touchscreen. By capitalizing on recent evidence that movements of a finger that points to a scene or text during visual exploration or reading may approximate eye fixations, we focus on recognition of written content and function words, pace of reading, and accuracy in reading comprehension. The analysis showed significant differences between typically developing and ASD children, with the latter group exhibiting greater variation in levels of reading ability, slower developmental pace in reading speed, less accurate comprehension, greater dependency on word length and word frequency, less significant prediction-based processing, as well as a monotonous, steady reading pace with reduced attention to weak punctuation. Finger-tracking patterns provides evidence that ASD readers may fail to integrate single word processing into major syntactic structures and lends support to the hypothesis of an impaired use of contextual information to predict upcoming stimuli, suggesting that difficulties in perception may arise as difficulties in prediction.

Early Sensory Profile in Autism Spectrum Disorders Predicts Emotional and Behavioral Issues.

Background: Abnormal sensory reactivity is considered one of the diagnostic criteria for autism spectrum disorders (ASD) and has been associated with autism severity, poorer functional outcomes, and behavioral difficulties across the lifespan. Its early characterization could provide valuable insights into the processes favoring the instantiation of maladaptive behaviors. Objectives: The present study has two aims: (1) to describe the sensory profile of preschool children with ASD compared with an age-matched population of children with a diagnosis of language disorder (DLD) and typically developing (TD) control peers; (2) to explore within each group whether the sensory alterations play a predictive role in the instantiation of emotional and behavioral issues. Methods: The parents of 42 ASD, 18 DLD, and 56 TD filled out the Sensory Processing Measure­Preschool (SPM-P). To gather information on competencies, behaviors, and emotional problems of children, the Child Behavior Checklist 1½-5 (CBCL 1½-5) was also administered. Results: On the SPM-P, ASD and DLD samples generally had scores more compromised than control peers. The contrast between ASD and DLD was reflected in a higher (and highly significant) impairment on the social participation and hearing subscales, suggesting a greater sensitivity and a possible specificity of these scores for ASD. More importantly, linear regression analyses revealed a strong and predictive association for ASD children with SPM total scores explaining more than 50% of the variance of the CBCL 1½-5 total scores (p < 0.001). Conclusions: Our findings reinforce the need to detect the abnormal sensory profiles of ASD already at an early stage and during clinical evaluations. Due to the impact on the emotional and behavioral manifestations, such a procedure has significant clinical and social implications, potentially guiding the development of new interventions relying on multisensory strategies.

Haste Makes Waste: There Is No Solid Evidence to Translate the Use of Stem Cells into Clinical Practice for Children with Autism Spectrum Disorder.

Increasingly, private clinics around the world offer stem cell therapy as a therapeutic approach for autism spectrum disorder (ASD) [...].

The Effect of Sleep-Wake Routines on the Negative Emotional States and Aggressive Behaviors in Adults with Autism Spectrum Disorders (ASD) during the COVID-19 Outbreak.

Disruption in routine may be related to experiencing negative emotional states and to aggressive behaviors in individuals with Autism Spectrum Disorder (ASD). The lockdown because of COVID-19 contributed to the disruption of individuals' routines, including the sleep−wake cycle. The current study tested a relationship between the adherence to the sleep−wake routine and aggressive behaviors via the mediation role of negative emotional states (i.e., anxiety and anger). Forty-three parents of adults with ASD completed a web-based questionnaire about their life condition during the first lockdown (April−May 2020). Preliminary analyses showed a worsening in the adults' aggressive behaviors during the lockdown in comparison to before it (Z = −3.130; p = 0.002). In the mediation models, the relationship between the adherence to the sleep−wake routines and aggressive behaviors was significant. The models showed the hypothesized mediated relationships among the adherence to the sleep−wake routines, negative emotional states, and aggressive behaviors (Model 1: F (1, 41) = 10.478, p < 0.001; Model 2: F(1, 41) = 9.826, p = 0.003). The findings confirmed the potential protective role of the adherence to the sleep−wake routines for the emotional and behavioral adjustment of adults with autism. Theoretical and practical contributions of the study were discussed; indeed, our results may inform parent-coaching as well as intervention programs for individuals with ASD given that adequate sleep hygiene may contribute to improvements in internalizing/externalizing behaviors.

Oral Health Preventive Program in Patients with Autism Spectrum Disorder.

The aim of the study was to evaluate clinical hygienic parameters, patient collaboration, and dental habits in patients with ASD (autism spectrum disorder) before and after a tailored prevention program. A total of 100 patients (78 males and 22 females, mean age 8 ± 0.7 years old) was recruited, with ages ranging from 7 to 16 years old, and diagnoses of ASD. We evaluated the plaque index (IP), gingival index (IG), the dmft/DMFT, the frequency of tooth brushing, and the frequency of snacks for each patient. Patient behaviour was evaluated with the Frankl scale, and each patient was individually reassessed after five visits from the first one by the same operator. The t test was used to compare the parameters before and after the inclusion in the dedicated dental pathway. From T1 to T2 we found a significant improvement of the IP (p < 0.001), IG (p < 0.001), and the frequency of tooth brushing (p < 0.001). Concerning the frequency of snacks and the parameter dmft/DMFT, the differences in the observed averages were not significant (p > 0.05). The difference in collaboration between T1 and T2 evaluated by the Frankl scale was statistically significant (p < 0.001). It was found that the prevention program allowed a significant improvement in both clinical parameters and patient behaviour. The personalized digital supports can have a key role for success in familiarization and desensitization processes of patients affected by ASD, leading an increase in their collaboration.

Research-Based Intervention (RBI) for Autism Spectrum Disorder: Looking beyond Traditional Models and Outcome Measures for Clinical Trials.

The rising prevalence of Autism Spectrum Disorders (ASD) has led to a quickly increasing need for effective interventions. Several criteria and measures have been developed to critically assess these interventions with particular focus on the evaluation of the efficacy. Given the huge diversity of ASD symptoms and the different levels of severity across individuals, identifying a one size fits all intervention approach is challenging, and the question What works and for whom? Remains still unanswered. Why do we seem to be dragging our feet on this fundamental issue? The main aim of this paper is to answer this question through four non-alternative points. First, there are a scarce number of studies with a solid methodology. Secondly, most trials on intervention efficacy for ASD are designed exclusively in terms of behavioral outcomes. Thirdly, there is a reduced use of biologically oriented outcome measures. Fourthly, in most clinical trials, appropriate practices emerging from research evidence are not systematically applied. A strong effort to improve the methodology of clinical trials is mandatory for the future of autism research. The development of a research-based intervention (RBI) perspective aimed at better integrating: (a) evidence-based approaches; (b) more sensitive behavioral outcome measures; and (c) biomarkers, with the aim of increasing a more detailed clustering of phenotypes, may strongly improve our approach to a precision medicine.