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This study examines the last 10 years of medical literature on the benefits of cochlear implantation in children who are deaf or hard of hearing (DHH) with additional disabilities. The most recent literature concerning cochlear implants (CIs) in DHH children with additional disabilities was systematically explored through PubMed, Embase, Scopus, PsycINFO, and Web of Science from January 2012 to July 2023. Our two-stage search strategy selected a total of 61 articles concerning CI implantation in children with several forms of additional disabilities: autism spectrum disorder, cerebral palsy, visual impairment, motor disorders, developmental delay, genetic syndromes, and intellectual disability. Overall, many children with additional disabilities benefit from CIs by acquiring greater environmental sound awareness. This, in turn, improves non-verbal communication and adaptive skills, with greater possibilities to relate to others and to be connected with the environment. Instead, despite some improvement, expressive language tends to develop more slowly and to a lesser extent compared to children affected by hearing loss only. Further studies are needed to better appreciate the specificities of each single disability and to personalize interventions, not restricting the analysis to auditory and language skills, but rather applying or developing cross-culturally validated instruments able to reliably assess the developmental trajectory and the quality of life of DHH children with additional disabilities before and after CI. [ABSTRACT FROM AUTHOR]

The effectiveness of early intensive interventions for Autism Spectrum Disorder (ASD) is now well-established, but there continues to be great interindividual variability in treatment response. The purpose of this systematic review is to identify putative predictors of response to two different approaches in behavioral treatment: Early Intensive Behavioral Interventions (EIBI) and the Early Start Denver Model (ESDM). Both are based upon the foundations of Applied Behavioral Analysis (ABA), but the former is more structured and therapist-driven, while the latter is more naturalistic and child-driven. Four databases (EmBase, PubMed, Scopus and WebOfScience) were systematically screened, and an additional search was conducted in the reference lists of relevant articles. Studies were selected if participants were children with ASD aged 12–48 months at intake, receiving either EIBI or ESDM treatment. For each putative predictor, p-values from different studies were combined using Fisher's method. Thirteen studies reporting on EIBI and eleven on ESDM met the inclusion criteria. A higher IQ at intake represents the strongest predictor of positive response to EIBI, while a set of social cognitive skills, including intention to communicate, receptive and expressive language, and attention to faces, most consistently predict response to ESDM. Although more research will be necessary to reach definitive conclusions, these findings begin to shed some light on patient characteristics that are predictive of preferential response to EIBI and ESDM, and may provide clinically useful information to begin personalizing treatment. [ABSTRACT FROM AUTHOR]

Autism Spectrum Disorder (ASD) encompasses a clinical spectrum of neurodevelopmental conditions that display significant heterogeneity in etiology, symptomatology, and severity. We previously compared 30 young children with idiopathic ASD and 30 unrelated typically-developing controls, detecting an imbalance in several compounds belonging mainly to the metabolism of purines, tryptophan and other amino acids, as well as compounds derived from the intestinal flora, and reduced levels of vitamins B6, B12 and folic acid. The present study describes significant urinary metabolomic differences within 14 pairs, including one child with idiopathic ASD and his/her typically-developing sibling, tightly matched by sex and age to minimize confounding factors, allowing a more reliable identification of the metabolic fingerprint related to ASD. By using a highly sensitive, accurate and unbiased approach, suitable for ensuring broad metabolite detection coverage on human urine, and by applying multivariate statistical analysis, we largely replicate our previous results, demonstrating a significant perturbation of the purine and tryptophan pathways, and further highlight abnormalities in the "phenylalanine, tyrosine and tryptophan" pathway, essentially involving increased phenylalanine and decreased tyrosine levels, as well as enhanced concentrations of bacterial degradation products, including phenylpyruvic acid, phenylacetic acid and 4-ethylphenyl-sulfate. The outcome of these within-family contrasts consolidates and extends our previous results obtained from unrelated individuals, adding further evidence that these metabolic imbalances may be linked to ASD rather than to environmental differences between cases and controls. It further underscores the excess of some gut microbiota-derived compounds in ASD, which could have diagnostic value in a network model differentiating the metabolome of autistic and unaffected siblings. Finally, it points toward the existence of a "metabolic autism spectrum" distributed as an endophenotype, with unaffected siblings possibly displaying a metabolic profile intermediate between their autistic siblings and unrelated typically-developing controls. [ABSTRACT FROM AUTHOR]

In recent years, findings from genetic and other biological studies are starting to reveal the role of various molecular mechanisms that contribute to the etiology of ASD. The relevance is at least twofold: on the one hand, this domain may be more directly linkable to specific and traceable neurobiological abnormalities in comparison to other ASD domains falling within the broader realm of social cognition; on the other hand, abnormal sensory processing is increasingly emerging as a relevant source of maladaptive behaviors with measurable impact on the quality of life of individuals with ASD and their families. Despite these efforts, DNA variation alone is unlikely to explain the majority of phenotypic variance, since epigenetic variation is as efficient as deletions in down-regulating expression of critical ASD genes [[41]] and the modulation of ASD gene promoter methylation is emerging as a significant cause of association between ASD and many common SNPs [[42]]. These and other studies suggest that many of the synaptic genes found to be associated with ASD are expressed prenatally and throughout early development, spatially and temporally coinciding with synaptic organization in brain regions relevant for ASD. [Extracted from the article]

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with onset in early childhood. Currently, psychopharmacological treatment in ASD can improve many comorbid neurodevelopmental disorders, such as attention-deficit/hyperactivity disorder or aggressive behaviour, and the core symptoms of restricted and repetitive behaviours [[8]]. Given the heterogeneity regarding the ASD phenotype and its underlying etiology, such as diverse genetic variation and additional environmental risks with the related neurobiological mechanisms, discovering new pharmacological treatments for the condition is a huge challenge. [Extracted from the article]

In clinical settings, the information provided by genetic testing can explain the triggers and processes underlying clinical presentations, such as neurodevelopmental disorders, in up to one third of affected individuals. However, translating this knowledge into better and more personalized clinical management to many appears a distant target. This article presents three paradigmatic cases to exemplify how this translational effort can, at least in some instances, be undertaken today with very positive results: (a) a young girl carrying a chr. 16p11.2 duplication can be screened using targeted exams and undertake therapeutic/preventive interventions related to her genetic diagnosis; (b) a 13-year-old boy with intellectual disability and autism spectrum disorder carries a chr. 11q14.1 deletion, partly spanning the DLG2 gene important for synaptic function, and gained over 20 I.Q. points ostensibly due to carbolithium, prescribed in the absence of affective symptoms, exclusively following the pathophysiology pointed out by the genetic results; (c) a 58-year-old woman carries a COL3A1 gene variant responsible for the vascular form of Ehler–Danlos syndrome with colon rupture. Detection of this variant in six members of her extended family allows for better clinical management of the proband and targeted genetic counselling for family members at risk of this connective tissue disorder. The unprecedented flow of genetic information available today through new technologies, if interpreted in the light of current knowledge in clinical diagnosis and care of those with connective tissue disorders and neurodevelopmental disturbances, in biology and in neuropsychopharmacology, can promote better clinical and pharmacological treatment, disease surveillance, and management provided and incorporated into the clinical setting. [ABSTRACT FROM AUTHOR]

Organophosphate compounds (OPs) interfere with neurodevelopment and are neurotoxic for humans and animals. They are first biotransformed to the more toxic oxon form, and then hydrolyzed to specific metabolites by the enzyme paraoxonase/arylesterase, encoded by the gene PON1 located on human chr. 7q21.3. In autism spectrum disorder (ASD) and in attention-deficit/hyperactivity disorder (ADHD), a correlation between OP exposure and disease onset has been reported. In this case-control study, we aimed to replicate our previous work showing reduced levels of serum PON1 arylesterase activity in Italian and Caucasian-American ASD samples, and to extend our analysis to other neurodevelopmental disorders, namely ADHD and developmental language disorder (DLD), also known as specific language impairment (SLI). The arylesterase activity, measured using standard spectrophotometric methods, is significantly reduced in the ADHD, and not in the ASD sample compared with the controls. Our previous results seemingly stem from spuriously high arylesterase levels in the former control sample. Finally, genotyping SNPs rs705379 and rs662 using TDI-FP, a significant effect of rs705379 alleles on the serum arylesterase activity is observed in all of the subgroups tested, regardless of diagnosis, as well as a lack of association between PON1 gene polymorphisms and ASD/ADHD susceptibility in the Italian population. In summary, the serum arylesterase activity is reduced in children and adolescents with ADHD, and this reduction is not due to the functional PON1 gene variants assessed in this study. Based on previous literature, it may more likely reflect enhanced oxidative stress than specific genetic underpinnings. [ABSTRACT FROM AUTHOR]

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction/communication, stereotypic behaviors, restricted interests, and abnormal sensory-processing. Several studies have reported significantly elevated urinary and foecal levels of p-cresol in ASD children, an aromatic compound either of environmental origin or produced by specific gut bacterial strains. Methods: Since p-cresol is a known uremic toxin, able to negatively affect multiple brain functions, the present study was undertaken to assess the effects of a single acute injection of low- or high-dose (1 or 10 mg/kg i.v. respectively) of p-cresol in behavioral and neurochemical phenotypes of BTBR mice, a reliable animal model of human ASD. Results: P-cresol significantly increased anxiety-like behaviors and hyperactivity in the open field, in addition to producing stereotypic behaviors and loss of social preference in BTBR mice. Tissue levels of monoaminergic neurotransmitters and their metabolites unveiled significantly activated dopamine turnover in amygdala as well as in dorsal and ventral striatum after p-cresol administration; no effect was recorded in medial-prefrontal cortex and hippocampus. Conclusion: Our study supports a gene x environment interaction model, whereby p-cresol, acting upon a susceptible genetic background, can acutely induce autism-like behaviors and produce abnormal dopamine metabolism in the reward circuitry. [ABSTRACT FROM AUTHOR]