Andrea De Giacomo

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition with wide differences in cognitive, behavioral, and adaptive outcomes across the lifespan. Current evidence suggests that part of this heterogeneity may be related to interactions among genetic susceptibility, environmental exposures, and immune processes acting during important periods of brain development. This narrative review examines the molecular and cellular mechanisms through which immune dysregulation and autoimmunity may contribute to neurodevelopmental variability in ASD. It also explores possible links with age-related neuropsychological trajectories. Main topics include maternal immune activation, maternal brain-reactive autoantibodies, cytokine signaling, peripheral immune cell changes, microglial and astrocytic function, complement-mediated synaptic remodeling, and gut–immune–brain pathways. These mechanisms are discussed in relation to language, attention, executive functions, sensory processing, social cognition, emotional regulation, adaptive functioning, and psychiatric comorbidity from childhood to adulthood. Current evidence supports immune dysfunction as a possible modifier of ASD phenotypes rather than a universal or isolated cause. Direct longitudinal evidence linking specific immune profiles to defined neuropsychological trajectories is still limited, especially in adults. Integrating molecular, immunological, and neuropsychological data may help identify biologically meaningful ASD subgroups and support future biomarker development, developmental stratification, and more personalized therapeutic approaches.

Background: 22q11.2 deletion syndrome (22q11.2 DS) is a rare genetic syndrome characterized by high phenotypic variability, with an incidence of approximately 1:4000 live births. Most of the existing literature consists of case reports or case series, making it challenging to obtain large cohorts for data comparison and drawing generalizable conclusions. Aim: The aim of this article is to share the clinical experience of patients with 22q11.2 DS who were previously evaluated by Child Neuropsychiatry and underwent odontoiatric procedures at the Dental Unit of the Policlinico di Bari. Methods: We report three clinical cases of pediatric patients with 22q11.2 DS who were managed at the University Dental Unit of the Policlinico di Bari for dental procedures, including pre/post-treatment images and child neuropsychiatric characteristics. Results: Cleft lip and cleft palate are the most commonly encountered facial malformations. Enamel hypoplasia and hypomineralizations, caries, dental agenesis, and hypodontia are reported with variable frequency in almost all studies considering the oral health of these patients. Our experience is coherent with the data present at the moment. The clinical examinations showed diffuse hypomineralization and several caries, concordant with the literature. One patient received moderate sedation and another received general anesthesia; oral prophylaxis, fluoride application, pulp therapy, extractions of hopeless teeth and restorations of carious and hypomineralized teeth were performed. Conclusions: 22q11.2 DS is a genetic condition with a variable prognosis, but current trends show that patients often reach adulthood, primarily due to advancements in cardiology, which was previously the leading cause of mortality in these patients. From this perspective, collaboration among various medical specialties is crucial to implement holistic patient management programs and early interventions.

Background: Autism Spectrum Disorders (ASD) are neurodevelopmental disorders characterized by repetitive behaviors and social interaction deficits. While the severity of ASD is classified into levels (1–3) by the DSM-5, reliable circulating biomarkers to differentiate these levels are lacking. This retrospective pilot study examines plasma amino acid levels in children with ASD to identify the potential biomarkers of disease severity. Methods: Plasma samples from 30 children diagnosed with ASD (24 males, 6 females, aged 3–12 years) were analyzed. Participants were stratified into two groups based on the Autism Diagnostic Observation Schedule Calibrated Severity Score (ADOS CSS): Group 1, presenting with mild symptoms (Level 1, n = 11), and Group 2, characterized by moderate-to-severe symptoms (Levels 2–3, n = 19). This was further confirmed by the identification of electroencephalogram (EEG) anomalies (21.1%) and magnetic resonance imaging (MRI) abnormalities (5.3%), which were detected exclusively in Group 2 and absent in Group 1. Amino acid levels were measured by ion-exchange chromatography. Statistical analyses (Mann–Whitney U test and chi-square test) were used to compare AA levels between groups. Results: Statistically significant differences were observed in the levels of phosphoethanolamine, aspartic acid, and glutamic acid between the two groups. These amino acids (AA) were significantly higher in the moderate-to-severe symptoms group (Levels 2–3) compared to the mild symptoms group (Level 1) (p < 0.05). All AA values remained within age-appropriate reference ranges. Conclusions: Plasma levels of phosphoethanolamine, aspartic acid, and glutamic acid may serve as potential biomarkers for ASD severity in children. Results from this exploratory analysis suggest that AA profiling could differentiate ASD severity and identify specific metabolic pathways, such as excitatory neurotransmission and phospholipid turnover. Further studies with larger cohorts are necessary to validate these findings and explore the role of AAs in ASD pathophysiology.

Background: Paediatric-onset Multiple Sclerosis (POMS) is a rare, highly active disease requiring timely disease-modifying therapy. Objectives: This trial compared the efficacy and safety of intramuscular (i.m.) Interferon beta-1a (IFN-beta 1a) and subcutaneous (s.c.) Glatiramer Acetate (GA). Methods: A 96-week, Phase IIIb, multicenter, open-label randomized trial enrolled 30 participants (ages 12–17). Patients were randomized into two groups: 15 received i.m. IFN-beta 1a, and 15 received s.c. GA. The primary endpoint was MRI disease activity-free status; secondary outcomes included annualized relapse rate (ARR), time to first relapse, Expanded Disability Status Scale (EDSS), cognitive and fatigue scores, and quality of life. Results: The groups differed by age but not sex. MRI disease activity-free status did not differ (p = 0.09). ARR was significantly lower in the GA group (0.20; 95% CI 0.08–0.42) than in the IFN-beta 1a group (0.57; 95% CI 0.31–0.95, p = 0.02). EDSS, cognitive, fatigue, and quality-of-life scores were comparable. Notably, 50% of GA patients and 30% of IFN-beta 1a patients switched to higher efficacy treatments. Conclusions: Both treatments showed similar efficacy and safety, but early high-efficacy therapy may be preferable for POMS management. Trial Registration: EudraCT Number: 2017–005129-18. https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-005129-18/IT

Less socially adaptive behaviors have often been underestimated in university students, with limited research addressing their impact on academic functioning. This study aimed to identify distinct profiles of social functioning difficulties in university students and to examine their associations with academic engagement, learning difficulties, and psychological distress. A cross-sectional, web-based survey was conducted with 540 undergraduate university students (mean age = 23.06, SD = 6.53; 89.7% female). Participants completed standardized self-report assessments of social functioning (SRS-2), academic engagement (SAES), learning difficulties (Vinegrad Plus), and psychological distress (GAD-7, PHQ-9). Latent profile analysis (LPA), based on ASD-related traits, revealed two latent profiles: one reflecting non-social functioning difficulties (311 participants, 57.6%—Profile 1) and another reflecting social functioning difficulties (229 participants, 42.4%—Profile 2), while binomial regression analyses examined their associations with academic outcomes. Participants in Profile 2 scored significantly higher than those in Profile 1 across all SRS-2 variables—awareness, cognition, communication, motivation, and restricted interests and repetitive behavior (p = 0.001)—indicating greater overall functioning in these domains. Students in the Non-social functioning difficulties profile showed higher levels of academic engagement in all areas. In contrast, students in the Social functioning difficulties profile experienced more self-reported learning challenges (p = 0.001), anxiety (p = 0.001), and depression (p = 0.001), underscoring the significant differences in social, academic, and emotional outcomes between the two profiles. These findings underscore the impact of vulnerability to social functioning difficulties on academic engagement, highlighting the need for tailored support systems within higher education settings.

Background. Sturge–Weber syndrome (SWS) is a rare non-hereditary neurovascular disorder characterized by capillary–venous malformations on the face, ocular vascular anomalies, and leptomeningeal capillary–venous malformations. Patients with SWS often experience cerebral perfusion impairment, increasing their risk for stroke-like episodes, seizures, and motor and cognitive impairments. Methods. We report the case of a 2-year-old boy diagnosed with SWS who developed a stroke-like episode following dye laser therapy under deep sedation. Results. Despite initial diagnostic challenges and persistent seizures, appropriate management led to full neurological recovery. Conclusions. This case highlights the importance of considering stroke-like episodes in children with SWS after stressful events such as medical procedures.

Studies have consistently shown that gender-diverse youth experience higher rates of internalizing disorders and self-harm behaviors (SH) compared to their cisgender peers. However, there is limited research on how body investment and emotion regulation influence these symptoms, especially in relation to the age of gender dysphoria (GD) presentation. Objectives: This study aimed to explore the relationship between the timing of GD presentation (early vs. late) and psychological distress in adolescents seeking gender affirmation (GA), specifically focusing on internalizing symptoms, emotion regulation, and body investment. The study also investigated how SH during the year preceding the request for gender affirmation might have impacted these factors. Methods: On a total of 80 adolescents (mean age: 14.88 years) at their first request for GA, participants were divided into two groups: early-presentation GD (EP-GD; mean age: 14.93 years) and late-presentation GD (LP-GD; mean age: 14.83 years). Among the sample, 60% exhibited SH. Internalizing symptoms, emotion regulation, and body investment were assessed using the Youth Self-Report (YSR), the Difficulties in Emotion Regulation Scale (DERS), and the Body Investment Scale (BIS). Results: Results revealed that LP-GD adolescents had significantly higher emotion dysregulation (ED), particularly in the Strategies domain of the DERS (p = 0.040), and more social problems in the YSR (p = 0.047) compared to EP-GD ones. SH were associated with higher internalizing symptoms, including anxiety, withdrawal, and somatic complaints (p < 0.03), as well as increased body dissatisfaction, particularly in the BIS Care and Protection dimensions (p = 0.044; p = 0.034). Conclusions: These findings supported the hypothesis that LP-GD adolescents and youths with a history of SH showed more pronounced emotion regulation difficulties and internalizing symptoms, further emphasizing the need for early intervention programs targeting both GD and co-occurring mental health problems.

: Panax ginseng is one of the most important remedies in ancient Eastern medicine. In the modern Western world, its reputation started to grow towards the end of the XIX century, but the rather approximate understanding of action mechanisms did not provide sufficient information for an appropriate use. Nowadays, Panax ginseng is frequently used in some pathological conditions, but the comprehension of its potential beneficial effects is still incomplete. The purpose of this study is to highlight the most recent knowledge on mechanisms and effects of ginseng active ingredients on the intestinal microbiota. The human microbiota takes part in the immune and metabolic balance and serves as the most important regulator for the control of local pathogens. This delicate role requires a complex interaction and reflects the interconnection with the brain- and the liver-axes. Thus, by exerting their beneficial effects through the intestinal microbiota, the active ingredients of Panax ginseng (glycosides and their metabolites) might help to ameliorate both specific intestinal conditions as well as the whole organism's homeostasis.

Background/Objectives: Autism Spectrum Disorder (ASD) is a lifelong neurodevelopmental condition characterized by social communication impairments and repetitive behaviors. Recent reports show that one in thirty-six 8-year-old children are autistic, signifying a considerable public health concern. According to previous studies, emotional dysregulation (ED) affects 50–60% of individuals with ASD and includes symptoms such as poor emotional control, heightened reactivity, and a low frustration tolerance. The main aims of the current study are to investigate the prevalence of ED among autistic preschoolers (below 6 years of age) and to assess the impacts of gender and intellectual disability on their emotional dysregulation profile. Methods: Data have been collected from three children’s research hospitals in Italy (IRCCS Stella Maris Foundation, Stella Maris Mediterraneo Foundation, and IRCCS Bambino Gesù). Parents of 825 autistic pre-schooled children (mean age: 39.68 months, SD: 10.51 months) completed a general questionnaire and the Child Behaviour Checklist (CBCL), a reliable caregiver-reported assessment tool which provides a dysregulation profile. Results: A total of 30% of the children displayed a severe-to-moderate ED (emotional dysregulation) profile, with these children exhibiting significantly higher emotional–behavioral problems compared to those without ED. Males with ED exhibited greater emotional reactivity than females with ED. However, no significant relationships were found between ED and age, autism severity (ADOS-2), or intellectual disability. Conclusions: The results underline the importance of early, tailored interventions to face emotional challenges in young children with ASD, potentially improving long-term outcomes for this population.

Purpose: Recent literature has focused attention on the presence of autistic-like symptoms in children with Attention Deficit/Hyperactivity Disorder (ADHD), who often exhibit social difficulties, posing challenges for a distinct clinical diagnosis. The current study aimed to identify the specific pattern of autistic symptoms in subjects with ADHD or Autistic Spectrum Disorder (ASD), examining similarities or differences at both the domain and individual item levels. Patients and Methods: In this study, we enrolled 43 school-age children divided into the following: the ADHD group (n=25) consisted of children initially referred for ASD symptoms but subsequently clinically diagnosed with ADHD, and the ASD group consisted of 18 children with ASD. We used the Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2), to examine relative differences in the presence of symptoms such as deficits in communication and social interaction, and restricted and repetitive behaviors in these two groups. Comparison between groups was conducted to explore differences in IQ, age, ADOS-2 domains, and externalizing and internalizing problems among the groups. Results: We found significant differences between the groups when comparing summary scores of ADOS-2 domains (Social Affect, Restricted and Repetitive Behavior, and Total Score). Interestingly, at the individual item level, the ADHD group exhibited a similar level of atypical behaviors compared to the ASD group in two items related to the social-communication area: “Pointing” and “Gestures”. Additionally, the frequencies of “Stereotyped/idiosyncratic words or phrases”, “Mannerisms”, and “Repetitive interests and behaviors” also showed similarities between groups. Conclusion: These findings indicate the importance of exploring and developing potential transdiagnostic domains that could be targeted for treatments specifically designed for children with ADHD.