SNAP-25 Polymorphisms in Autism Spectrum Disorder: A Pilot Study towards a Possible Endophenotype.

While there is substantial agreement on the diagnostic criteria for autism spectrum disorder, it is also acknowledged that it has a broad range of clinical presentations. This can complicate the diagnostic process and aggravate the choice of the most suitable rehabilitative strategy for each child. Attentional difficulties are among the most frequently reported comorbidities in autism spectrum disorder. We investigated the role of SNAP-25 polymorphisms. Synaptosome-associated protein 25 (SNAP25) is a presynaptic membrane-binding protein; it plays a crucial role in neurotransmission and has already been studied in numerous psychiatric disorders. It was also seen to be associated with hyperactivity in children with autism spectrum disorder. We collected clinical, behavioral and neuropsychological data on 41 children with a diagnosis of autism spectrum disorder, and then genotyped them for five single-nucleotide polymorphisms of SNAP-25. Participants were divided into two groups according to the Autism Diagnostic Observation Schedule (ADOS-2) Severity Score. In the group with the highest severity score, we found significant associations of clinical data with polymorphism rs363050 (A/G): children with the GG genotype had lower total IQ, more severe autistic functioning and more attentional difficulties. Our research could be the starting point for outlining a possible endophenotype among patients with autism spectrum disorder who are clinically characterized by severe autistic functioning and significant attentional difficulties.

The Role of SNAP-25 in Autism Spectrum Disorders Onset Patterns.

Autism spectrum disorders (ASD) can present with different onset and timing of symptom development; children may manifest symptoms early in their first year of life, i.e., early onset (EO-ASD), or may lose already achieved skills during their second year of life, thus showing a regressive-type onset (RO-ASD). It is still controversial whether regression represents a neurobiological subtype of ASD, resulting from distinct genetic and environmental causes. We focused this study on the 25 kD synaptosomal-associated protein (SNAP-25) gene involved in both post-synaptic formation and adhesion and considered a key player in the pathogenesis of ASD. To this end, four single nucleotide polymorphisms (SNPs) of the SNAP-25 gene, rs363050, rs363039, rs363043, and rs1051312, already known to be involved in neurodevelopmental and psychiatric disorders, were analyzed in a cohort of 69 children with EO-ASD and 58 children with RO-ASD. Both the rs363039 G allele and GG genotype were significantly more frequently carried by patients with EO-ASD than those with RO-ASD and healthy controls (HC). On the contrary, the rs1051312 T allele and TT genotype were more frequent in individuals with RO-ASD than those with EO-ASD and HC. Thus, two different SNAP-25 alleles/genotypes seem to discriminate between EO-ASD and RO-ASD. Notably, rs1051312 is located in the 3' untranslated region (UTR) of the gene and is the target of microRNA (miRNA) regulation, suggesting a possible epigenetic role in the onset of regressive autism. These SNPs, by discriminating two different onset patterns, may represent diagnostic biomarkers of ASD and may provide insight into the different biological mechanisms towards the development of better tailored therapeutic and rehabilitative approaches.

Alterations of natural killer cells activatory molecules phenotype and function in mothers of ASD children: a pilot study.

Introduction: Autism spectrum disorder (ASD) is accompanied by complex immune alterations and inflammation, and the possible role played by Natural Killer (NK) in such alterations is only barely understood. Methods: To address this question we analysed activating and inhibitory NK receptors, as well as NK cells phenotype and function in a group of mothers of children who developed ASD (ASD-MO; N=24) comparing results to those obtained in mothers of healthy children who did not develop (HC-MO; N=25). Results: Results showed that in ASD-MO compared to HC-MO: 1) NK cells expressing the inhibitory receptor ILT2 are significantly decreased; 2) the activating HLA-G14bp+ polymorphism is more frequently observed and is correlated with the decrease of ILT2-expressing cells; 3) the CD56bright and CD56dim NK subsets are increased; 4) IFNγ and TNF production is reduced; and 5) perforin- and granzymes-releasing NK cells are increased even in unstimulated conditions and could not be upregulated by mitogenic stimulation. Discussion: Results herein reinforce the hypothesis that ASD relatives present traits similar to, but not as severe as the defining features of ASD (Autism endophenotype) and identify a role for NK cells impairment in generating the inflammatory milieu that is observed in ASD.

WISC-IV intellectual profiles in Italian children with self-limited epilepsy with centrotemporal spikes.

OBJECTIVE: This study aimed to describe the intellectual profile based on the Wechsler Intelligence Scale for Children 4th edition (WISC-IV) in children with self-limited epilepsy with centrotemporal spikes (SeLECTS), with an attempt to define possible predictive epilepsy-related variables of cognitive performance. METHODS: The WISC-IV was assessed in 161 children with SeLECTS and their cognitive profiles were compared to a matched sample of healthy control children. RESULTS: Children with SeLECTS performed within normal range across all indices, demonstrating particular strength based on the Perceptual Reasoning Index. Compared to healthy control children, we observed a significant difference in performance based on the Full Scale Intelligence Quotient, Verbal Comprehension Index and Processing Speed Index. Regarding epilepsy-related variables, earlier onset of epilepsy, use of anti-seizure medications, the presence of neurodevelopmental disorders, a higher frequency of seizures, and a longer treatment duration were associated with an overall lower level of performance. SIGNIFICANCE: Children with SeLECTS performed within the average range for cognitive assessment based on the WISC-IV, demonstrating that children had normal levels of global intelligence. However, compared to healthy control children, children with SeLECTS showed a slightly lower level of performance. Reasoning skills represented the relative strengths in children with SeLECTS. Predictors of intellectual performance in patients with SeLECTS include epilepsy-related variables and neurodevelopmental comorbidities.

The Family Caregiving Environment Associates with Adolescent Patients' Severity of Eating Disorder and Interpersonal Problems: A Cross-Sectional Study.

The quality of family interactions may be a critical factor for restrictive eating disorders (REDs). Adolescent patients with RED have interpersonal problems that can be inferred by observing their behaviours during family interactions. To date, the assessment of the association among RED severity, interpersonal problems, and patients' interactive behaviours in the family is partially explored. This cross-sectional study aimed to explore how adolescent patients' interactive behaviours observed during the Lausanne Trilogue Play-clinical version (LTPc) were associated with both RED severity and interpersonal problems. Sixty adolescent patients completed the EDI-3 questionnaire to assess RED severity using the Eating Disorder Risk Composite (EDRC) and Interpersonal Problems Composite (IPC) subscales. Moreover, patients and their parents took part in the LTPc, and patients' interactive behaviours were coded as participation, organization, focal attention, and affective contact in all the LTPc four phases. A significant association emerged between patients' interactive behaviours during the LTPc triadic phase and both EDRC and IPC. Better patients' organization and affective contact significantly correlated with lower RED severity and fewer interpersonal problems. These findings suggest that investigating the quality of family relationships and patients' interactive behaviours may contribute to better identifying adolescent patients at risk for more severe conditions.

Marked intrafamilial variability of clinical and neuroimaging manifestations in NFIB-related developmental disorder.

NFIB belongs to the nuclear factor I (NFI) family of transcription factors that, by activating or repressing gene expression during embryogenesis, has a relevant role in the development of several organs including the brain. Heterozygous pathogenic variants of NFIB have recently been associated with developmental delay and mild-to-moderate intellectual disability, macrocephaly, nonspecific facial dysmorphisms, and corpus callosum dysgenesis. We identified a heterozygous missense variant in the NFIB gene in a 15-year-old boy with neurodevelopmental disorder and brain malformations, who inherited the variant from his substantially healthy mother presenting only minor physical and neuroanatomical defects.

Ethics of Bariatric Surgery in Adolescence and Its Implications for Clinical Practice.

Obesity is increasingly prevalent among adolescents. Clinical and research data support the use of bariatric surgery (BS) as a treatment option for severely obese adolescents, with good results in terms of weight loss, improvement or resolution of comorbidities, and compliance to follow up. Nevertheless, concerns still remain, with significant disparities among countries and ethical concerns mainly raised by performing an irreversible and invasive procedure in adolescence, with potential life-long alterations. In this context, the purpose of this narrative review was to discuss the main current ethical challenges in performing BS in adolescence and to inform appropriate clinical management in the field. The core ethical principles of autonomy, beneficence, nonmaleficence, and justice were revised in terms of patient-centered healthcare through the lens of psychosocial implications. The review concludes with a discussion regarding the potential directives for future research for effective, patient-centered, and ethical management of obesity in the adolescent population.

Empathy and behavior in children affected by autism spectrum disorders.

BACKGROUND: Many studies have already shown that individuals suffering from autism spectrum disorders (ASD) present low levels of empathy: in fact, reduced emotional reciprocity is considered a clinically significant indicator of autistic functioning. We decided to investigate the role of empathy in determining pathological behaviors in children affected by ASD considering parents' point of view; and to evaluate the presence of differences between mothers and fathers' perception of their child's empathy and behaviors. METHODS: We compared empathy levels in a sample of 58 patients with ASD as reported by a parent-filled questionnaire with the results of a global evaluation conducted by means of play observations, clinician-rated scales, a semistructured interview with both caregivers and parent-filled questionnaires. RESULTS: The majority of ASD patients have low levels of empathy according to both parents' points of view; noteworthy, mothers and fathers are highly concordant in this respect. Children's levels of empathy negatively correlate with many behavioral problems, both internalizing and externalizing. Furthermore, we found that mothers tend to perceive more internalizing problems, while fathers are more willing to notice externalizing ones. CONCLUSIONS: Involving both caregivers in children's diagnostic assessment could deepen patient's evaluation and finally the therapeutic results. Mothers and fathers seem to be highly consistent in describing the psychological characteristics of their child, but not in respect to symptoms.

How parental levels of empathy and alexithymia influence their perception of child's behavior.

BACKGROUND: Literature states that parents of individuals affected by autism spectrum disorder (ASD) can present social and cognitive deficits, restricted behavior patterns and psychiatric difficulties, without meeting standard diagnostic criteria for ASD ("broader autism phenotype"). We explored the relationship between parenting of children affected by ASD and levels of empathy and lack of emotion understanding (alexithymia). METHODS: We enlisted 58 families in which a child was affected by ASD. Parents' empathy and alexithymia were respectively assessed by means of Empathy Quotient (EQ) and Toronto Alexithymia Scale (TAS-20). Additionally, we included the assessment of the perception of children's behavior through the Child Behavior Checklist (CBCL). RESULTS: Our findings suggest that most parents have normal empathy and do not show significant alexithymia. We found lower EQ and higher TAS-20 scores being more frequent in fathers. Moreover, each parent's empathy degree negatively relates to his/her alexithymia and vice versa, showing that these two features are inversely correlated. Our study unveiled a strong correlation between maternal empathy and alexithymia and child's externalizing problems, as reported by mothers. CONCLUSIONS: Our data reveal differences in mothers and fathers' empathy and alexithymia profiles and confirm the importance of considering both parents' points of view either in the diagnostic and the therapeutic interventions. Parental empathy and alexithymia levels not only play a fundamental role in the evaluation of child's difficulties but can also influence the development of a good relationship with the child for what concerns affective resonance.

Bariatric Surgery: Psychosocial Aspects and Quality of Life.

Obesity is a major worldwide health problem, causing an ongoing and decades-long pandemic, which the WHO has termed the "global obesity epidemic", concurrent with the COVID-19 pandemic [...].

GC1f Vitamin D Binding Protein Isoform as a Marker of Severity in Autism Spectrum Disorders.

Autism spectrum disorders (ASD) are characterized by a wide spectrum of clinical, behavioral, and cognitive manifestations. It is, therefore, crucial to investigate possible biomarkers associated with specific ASD phenotypes. Ample literature suggests a possible role for vitamin D (VD) in influencing ASD clinical phenotypes. We analyzed three vitamin D binding protein gene (DBP) functional polymorphisms (rs2282679, rs7041, and rs4588), which are involved in the modulation of vitamin D serum concentration in 309 ASD children and 831 healthy controls. Frequency comparisons of single nucleotide polymorphisms (SNPs) alleles, genotypes, and GC isoforms (GC1f, G1s, and GC2)­generated by the combination of rs7041 and rs4588 alleles­were correlated with ASD diagnostic, behavioral, and functioning scales. The GC1f isoform was significantly more frequent in ASD compared with controls (18.6% vs. 14.5% pc = 0.02). Significantly higher scores for item 15 of the Childhood Autism Rating Scale (CARS) and lower ones for the Children's Global Assessment Scale (CGAS) functioning scales were seen in ASD carrying the GC1f isoform. In GC phenotype analysis, a gradient of severity for overall CARS scores and CARS item 15 was observed, with scores decreasing according to the presence of GC1f-GC1f > GC1f-GC1s > GC1s-GC1s > GC1f-GC2 > GC2-GC2 isoforms. Similarly, lower CGAS scores were seen in carriers of the GC1f-GC1f isoform, whereas higher scores were present in those carrying GC2-GC2 (p = 0.028). This is the first study to evaluate possible relationships between GC variants and the different aspects of ASD in Italian ASD children. Results, although needing to be validated in ampler cohorts, suggest that the GC1f isoform could be a marker of severity in ASD that may be useful in establishing the intensity of therapeutic and rehabilitative protocols.

Family Dysfunctional Interactive Patterns and Alexithymia in Adolescent Patients with Restrictive Eating Disorders.

Adolescents diagnosed with Restrictive Eating Disorders (REDs) are at risk for alexithymia. REDs patients' families show dysfunctional interactive patterns, and childhood family environment influences alexithymia development. We aimed to assess the relationship between family dysfunctional interactive patterns and patients' alexithymia in a sample of adolescents diagnosed with REDs. Forty-five patients and their parents were enrolled. They participated in the clinical version of the Lausanne Triadic Play (LTPc), a standardized observational procedure to assess family functioning. We used the self-report questionnaire Toronto Alexithymia Scale (TAS-20) to assess patients' alexithymia. The TAS-20 provides a multi-factorial measure of patients' alexithymia: Difficulty in Identifying Feelings, DIF; Difficulty in Describing Feelings, DDF; Externally-oriented Thinking, EOT) and a total (TOT) score. DDF and EOT scores were significantly higher than DIF score. Patients' families showed dysfunctional interactive patterns, with a predominance of collusive alliance. Patients from families characterized by collusive alliance had higher TOT scores compared to counterparts from families exhibiting a different interactive dysfunctional pattern. In families characterized by a collusive triadic alliance, the dysfunctional interactive pattern was linked with the risk of alexithymia in patients with REDs. Assessment of family relationships should be included in the routine consultation with adolescent patients affected by REDs.

Recent Advances in Child and Adolescent Psychiatry.

The field of child and adolescent psychiatry is receiving growing attention, although a number of local differences still exist in terms of academic curricula, board certifications and even definitions of what is to be considered part of this field or not [...].

Conclusive Thoughts for a New Beginning.

When I was asked to name this Special Issue, I was both honored and worried, as being appointed the Guest Editor was a significant achievement and honor [...].

Effectiveness of Short-Term Psychodynamic Psychotherapy in Preadolescents and Adolescents Affected by Psychiatric Disorders.

OBJECTIVE: Few studies have explored the effectiveness of short-term psychodynamic psychotherapy in children and adolescents. We aimed to investigate its efficacy in a heterogeneous group of young patients. We also wanted to check any relation between the improvement and patients' age, sex, or diagnostic category. METHODS: We recruited a group of 123 patients (11 to 19 years old) with a diagnosis of psychiatric disorders confirmed by Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS). All participants received eight sessions of psychodynamic psychotherapy ("Brief Individuation Psychotherapy" by Senise). They were assessed using the Clinical Global Impression (Severity at baseline, Improvement after treatment), and the Children's Global Assessment Scale (C-GAS). RESULTS: We found a clinically meaningful improvement in most patients (CGI-I 3 or lower; 79 out of 123, 64.2%) and a statistically significant improvement in the overall functioning (as measured by the C-GAS; p<0.001). We found no effect of age or sex of the patient on results obtained; patients with an externalizing disorder had significantly poorer results. CONCLUSION: Our study, although lacking a control group, supports the possibility to use short-term psychodynamic psychotherapy in the treatment of psychiatric disorders in preadolescents and adolescents affected by psychiatric disorders.

Ketogenic Dietary Therapies in Patients with Autism Spectrum Disorder: Facts or Fads? A Scoping Review and a Proposal for a Shared Protocol.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with increasing incidence. An expanding body of literature is examining connections between ASD and dietary interventions. Existing reports suggest a beneficial effect of ketogenic dietary therapies (KDTs) in improving behavioral symptoms in ASD. In this context, the purpose of this scoping review was to identify and map available evidence in the literature about the feasibility and potential efficacy of KDTs in pediatric patients with ASD and to inform clinical practice in the field. Moreover, based on the resulting data from the literature review, we aimed to provide a shared protocol to develop a personalized KDT intervention in patients with ASD. A comprehensive and structured web-based literature search was performed using PubMed and Scopus and it yielded 203 records. Seven papers were finally selected and included in the review. Data were abstracted by independent coders. High variability was identified in study designs and dietary aspects emerged among selected studies. Results supported the effectiveness of KDTs in promoting behavioral improvements. Clinical recommendations on which patients may benefit most from KDTs implementation and difficulties in dietary adherence were discussed.

Reading Skills of Children with Dyslexia Improved Less Than Expected during the COVID-19 Lockdown in Italy.

Following school closures due to the SARS-CoV-2 pandemic, for some months, children received only distance learning. The effects of this approach, however, are not clear for children with dyslexia. We conducted a cross-sectional comparison between children with and without dyslexia after the so-called "lockdown" and a comparison between pre- and post-lockdown parameters in children with dyslexia. We recruited sixty-five children with dyslexia (dyslexia group, DG) from an outpatient facility in Pavia (Lombardy, Italy) and fifty-two children without specific learning disabilities as the control group (CG) from summer camps in the same province. We performed neuropsychological tests to explore reading skills and an ad hoc questionnaire to explore how parents and children had experienced the measures taken to reduce spreading of SARS-CoV-2 infection. Between 59 to 63% of children with dyslexia did not reach the average expected increase of reading skills. According to their parents, they also showed greater social isolation and fewer worries about the pandemic and the school's closure. Our data indicate that children with dyslexia are at increased risk of consequences on their learning potential in case of school closure. They also seem to have a peculiar psychological experience of school closure. Specific interventions should therefore be provided to minimize the risk of negative effects on global development.

Lactobacillus plantarum PS128 and Other Probiotics in Children and Adolescents with Autism Spectrum Disorder: A Real-World Experience.

Autism Spectrum Disorder is a neurodevelopmental disorder. Recent data suggest that probiotics can reduce some symptoms of this disorder and Lactobacillus plantarum PS128 has been reported to be especially useful. We recruited a sample of 131 autistic children and adolescents (M:F = 122:19; age: 86.1 ± 41.1 months) and evaluated their changes after use of probiotics by mean of CGI. We found some significant improvements with very few side effects; these positive effects were more evident in younger children. Patients taking Lactobacillus plantarum PS128 had greater improvements and fewer side effects than those taking other probiotics. Our real-life data are consistent with existing literature showing a specific effect of Lactobacillus plantarum PS128 in Autism Spectrum Disorder.

Assessing Family Functioning Before and After an Integrated Multidisciplinary Family Treatment for Adolescents With Restrictive Eating Disorders.

The present study presents an investigation of family functioning in the families of adolescents with severe restrictive eating disorders (REDs) assessed before and 6 months after a multidisciplinary family treatment program that combined psychodynamic psychotherapy, parental role intervention, and triadic or family-centered interventions. Nutritional counseling and neuropsychiatric monitoring of the overall treatment and care process were also provided. Family functioning was assessed using the clinical version of the Lausanne Trilogue Play (LTPc), a semi-structured procedure for observing family dynamics, previously validated for this patient population. The LTPc is divided into four phases. In phase 1, the mother interacts with the patient while the father assumes the role of observer. In phase 2, the father plans an activity with the patient while the mother observes. In phase 3, all the family members interact. Finally, in phase 4, the parents talk while the adolescent observes. A significant change emerged in family functioning after the treatment, but only for the interactive phase 2, when the father is required to interact with the daughter while the mother silently observes. The results of this study suggest that a relatively brief multidisciplinary treatment program may significantly improve family functioning in the families of patients diagnosed with severe REDs. Although appropriate clinical trials are needed to further test the efficacy of this treatment, the results also reinforce the concept that treatment programs targeting the individual patient and both the parents should be a first-line approach in adolescents with severe REDs.