Search Results (569)

Background: Autism spectrum disorders (ASDs) comprise a neurodevelopmental disease marked by impaired social communication and repetitive activities. An imbalance between excitatory and inhibitory neurotransmitters, such as glutamate and GABA, may play a significant function in ASDs. The neurophysiological process behind epilepsy is abnormal neuronal excitatory firing in particular brain regions brought on by a lack of GABAergic inhibition. The study of GABAergic dysfunction could explain the substantial comorbidity with epilepsy or increased susceptibility to seizures observed in people with autism. Objective: This study analyzes molecular indicators directly and indirectly related to GABAergic inhibitory signaling in individuals with autism and healthy controls, with the purpose of uncovering probable diagnoses. Methods: The study included 46 male autistic participants and 26 age- and gender-matched healthy controls. Plasma levels of two chloride co-transporters (KCC2, NKCC1), and vitamin D3 were evaluated using ELISA. Results: Autistic individuals showed a significant drop in all three examined variables when compared to healthy controls. Statistical methods such as correlation, combined receiver operating characteristic (ROC) curve analysis, and multiple regression modeling were used to assess the diagnostic value and interrelationships of these biomarkers. A significant increase in the area under the curve was seen using the combined ROC curve analysis. The combined variables also exhibited significantly higher sensitivity and specificity as an index of high predictiveness values. Measurement of plasma levels of vitamin D status and chloride co-transporters (KCC2, NKCC1) in children with ASD may help to better understand how sleep disturbances and epilepsy as comorbidities of ASD linked to vitamin D deficiency and peculiar inhibitory/excitatory effects of GABA. Full article

Background: GM3 Synthase Deficiency (GM3SD) is a rare autosomal recessive neurodevelopmental disease characterized by recurrent seizures and neurological deficits. The disorder stems from mutations in the ST3GAL5 gene, encoding GM3 synthase (GM3S), a key enzyme in ganglioside biosynthesis. While enzyme deficiencies affecting ganglioside catabolism are well-documented, the consequences of impaired ganglioside biosynthesis remain less explored. Methods: To investigate GM3SD, we used a Human Embryonic Kidney 293-T (HEK293-T) knockout (KO) cell model generated via CRISPR/Cas9 technology. Lipid composition was assessed via high-performance thin-layer chromatography (HPTLC); glycohydrolase activity in lysosomal and plasma membrane (PM) fractions was enzymatically analyzed. Lysosomal homeostasis was evaluated through protein content analysis and immunofluorescence, and cellular bioenergetics was measured using a luminescence-based assay. Results: Lipidome profiling revealed a significant accumulation of lactosylceramide (LacCer), the substrate of GM3S, along with increased levels of monosialyl-globoside Gb5 (MSGb5), indicating a metabolic shift in glycosphingolipid biosynthesis. Lipid raft analysis revealed elevated cholesterol levels, which may impair microdomain fluidity and signal transduction. Furthermore, altered activity of lysosomal and plasma membrane (PM)-associated glycohydrolases suggests secondary deregulation of glycosphingolipid metabolism, potentially contributing to abnormal lipid patterns. In addition, we observed increased lysosomal mass, indicating potential lysosomal homeostasis dysregulation. Finally, decreased adenosine triphosphate (ATP) levels point to impaired cellular bioenergetics, emphasizing the metabolic consequences of GM3SD. Conclusions: Together, these findings provide novel insights into the molecular alterations associated with GM3SD and establish the HEK293-T KO model as a promising platform for evaluating potential therapeutic strategies. Full article

Background: Moderate and late preterm infants (32–36 weeks of gestation) are at significant risk of developmental impairments. Incidence of white matter lesions, which are associated with developmental impairments in very preterm infants, remains underreported in this population. This study aimed to assess the incidence and clinical risk factors associated with brain lesions, particularly white matter lesions, in moderate and late preterm infants using term-equivalent MRI. Methods: This prospective observational study included 195 preterm infants born at 32+0–36+6 weeks of gestation and admitted to a tertiary NICU between 2019 and 2020. MRI findings at term-equivalent age were evaluated. Clinical risk factors were analysed using logistic regression. Results: Among the 195 infants, 23.6% had brain lesions on MRI, with white matter lesions (73.9%), specifically punctate white matter lesions, being the most common form of lesions. Vaginal delivery (odds ratio (OR) = 3.102, 95% confidence interval (CI) = 1.250–7.696, p = 0.015), larger birth weight z-scores (OR = 1.702, 95% CI = 1.118–2.591, p = 0.013), and intubation (OR = 2.948, 95% CI = 1.269–6.850, p = 0.012) were significant risk factors for white matter lesions. Conclusions: White matter lesions, particularly punctate white matter lesions, are common in moderate and late preterm infants. These lesions are associated with perinatal factors suggestive of delayed transition and inflammation. Future research should focus on detailed clinical care measures and neurodevelopmental assessments to identify modifiable risk factors for brain injury. Full article

Vitamin B12 (cobalamin) plays a crucial role in neurodevelopment, particularly during pregnancy and early childhood. It is essential for DNA synthesis, red blood cell formation, and nervous system function. Maternal B12 levels are particularly important, as they influence fetal brain development. Inadequate maternal intake during pregnancy may lead to altered neurodevelopmental trajectories and increase the risk of ASD. Postnatally, insufficient dietary cobalamin in infants and young children could further contribute to cognitive and behavioral impairments. One potential mechanism linking low B12 levels to ASD involves its role in the gut microbiota balance. Dysbiosis, commonly observed in individuals with ASD, is associated with increased gut permeability, low-grade inflammation, and disruptions in the gut–brain axis, all of which may contribute to ASD symptoms. Additionally, B12 is essential for neurotransmitter metabolism, particularly in the synthesis of serotonin and dopamine, which regulate mood, cognition, and behavior. Cobalamin also plays a key role in neuronal myelination, which ensures efficient signal transmission in the nervous system. Disruptions in these processes could underlie some of the cognitive and behavioral features associated with ASD. Despite growing evidence, the link between B12 and ASD remains inconclusive due to inconsistent findings across studies. Research suggests that B12 levels may serve as a potential biomarker for disease progression and treatment response. However, many studies rely on single-time-point measurements, failing to account for individual variability, genetic predispositions, dietary intake, and environmental factors, all of which can influence B12 levels and ASD risk. Further longitudinal studies are needed to clarify this relationship. Full article

Hikikomori is a form of social withdrawal lasting more than 6 months with significant associated functional impairment. To date, numerous studies confirm the presence of this condition not only in Japan, where it was first described, but also globally abroad. This is an underestimated clinical condition, and it is emerging especially in adolescents and young adults, representing an increasing management problem for families and society. Prevalence ranges from 1.1% to 6.7%. Hikikomori can be associated with other neurodevelopmental disorders, such as Autism Spectrum Disorder (ASD). Indeed, ASD and hikikomori share numerous characteristics confirmed by functional neuroimaging studies that have highlighted in both conditions the presence of alterations in cerebral regions related to social functioning. We present a case report regarding the history of a 14-year-old girl with characteristics compatible with ASD and hikikomori. At present, there are no specific treatments approved for hikikomori in ASD patients. Further studies are necessary to understand the link between the two conditions, the boundary, and possible overlap. Full article

Background: The human brain relies on complex synaptic communication regulated by key genes such as SYNGAP1. SYNGAP1 encodes the GTPase-Activating Protein (SYNGAP), a critical synaptic plasticity and neuronal excitability regulator. Impaired SYNGAP1 function leads to neurodevelopmental disorders (NDDs) characterized by intellectual disability (ID), epilepsy, and behavioral abnormalities. These variants disrupt Ras signaling, altering AMPA receptor transport and synaptic plasticity and contributing to cognitive and motor difficulties. Despite advancements, challenges remain in defining genotype–phenotype correlations and distinguishing SYNGAP1-related disorders from other NDDs, which could improve underdiagnosis and misdiagnosis. Brain Gene Registry: The Brain Gene Registry (BGR) was established as a collaborative initiative, consolidating genomic and phenotypic data across multiple research centers. This database allows for extensive analyses, facilitating improved diagnostic accuracy, earlier interventions, and targeted therapeutic strategies. The BGR enhances our understanding of rare genetic conditions and is critical for advancing research on SYNGAP1-related disorders. Conclusions: While no FDA-approved treatments exist for SYNGAP1-related disorders, several therapeutic approaches are being investigated. These include taurine supplementation, ketogenic diets, and molecular strategies such as antisense oligonucleotide therapy to restore SYNGAP1 expression. Behavioral and rehabilitative interventions remain key for managing developmental and cognitive symptoms. Advancing research through initiatives like the BGR is crucial for refining genotype–phenotype associations and developing precision medicine approaches. A comprehensive understanding of SYNGAP1-related disorders will improve clinical outcomes and patient care, underscoring the need for continued interdisciplinary collaboration in neurodevelopmental genetics. Full article

Background: Newborns, including preterm infants, are capable of responding to pain. Recurrent pain exposure is associated with suboptimal motor development, cognitive impairments, abnormal brain growth, and maladapted nociceptive reactions. Problem: Current agents, primarily opioids and benzodiazepines, raise major concerns due to their adverse effects, including insufficient sedation or analgesia, withdrawal, depressed respiratory effort, tolerance, and occasional paradoxical agitation. Commonly used drugs such as midazolam and morphine have been shown to induce neuroapoptosis and neurodevelopmental abnormalities in animal studies. Evaluation—Dexmedetomidine: As a specific alpha-2 adrenergic agonist, dexmedetomidine causes a significantly lower reduction in breathing effort. It has over 800 times greater affinity for alpha-2 receptors compared to alpha-1 receptors. Common side effects include bradycardia and hypotension. Prolonged use may necessitate a transition to clonidine during the weaning process. Dexmedetomidine can be administered intravenously as a bolus or infusion or intranasally. Indications include sedation and analgesia for mechanical ventilation, therapeutic hypothermia, procedural premedication, and as an adjunct to inhalational anesthesia and nerve-blocking agents. Research across varying age groups has demonstrated that dexmedetomidine shortens periods of invasive ventilation and decreases the need for other sedatives. Neonatal studies suggest that dexmedetomidine may help accelerate the achievement of full enteral feeds and can be safely administered within specific dosage ranges without causing significant adverse events that would necessitate abrupt discontinuation. Conclusions: Dexmedetomidine can be used alone or in combination with other agents. By increasing the use of dexmedetomidine, it is possible to reduce the dosage of concurrent medications, thereby minimizing the risk of complications while still achieving the desired sedation and analgesia. Full article

Many neurobehavioral tests are used for the assessment of human-like behaviors in animals. Most of them were developed in rodents and are used for the assessment of animal models that mimic human neurodevelopmental and neuropsychiatric disorders (NDDs). We have described tests for assessing social behavior, social interaction, and social communication; tests for restricted and repetitive behaviors; tests for cognitive impairment, for sensory stimuli, for anxiety like behavior, and for motor coordination deviations. These tests are used to demonstrate autistic-like behavior as well as other NDDs. We described possible general pitfalls in the performance of such studies, as well as probable individual errors for each group of tests assessing specific behavior. The mentioned pitfalls may induce crucial errors in the interpretation of the results, minimizing the reliability of specific models of defined human NDD. It is imperative to minimize these pitfalls and use sufficient and reliable tests that can demonstrate as many of the traits of the human disorder, grade the severity of the specific deviations and the severity of the tested NDD by using a scoring system. Due to possible gender differences in the clinical presentations of NDD, it is important to carry out studies on males and females. Full article

Background/Objectives: Cerebral palsy (CP), often caused by early brain injury such as perinatal stroke or hemorrhage, is the most common lifelong motor disability. Early identification of at-risk infants and timely access to rehabilitation interventions are essential for improving long-term outcomes. The General Movements Assessment (GMA), performed in the first months of life, has high sensitivity and specificity to predict CP; however, the neurological correlates of general movements remain unclear. This analysis aimed to investigate the relationship between white matter integrity and general movements in infants with perinatal brain injury using advanced neuroimaging techniques. Methods: Diffusion-weighted MRI data were analyzed in 17 infants, 12 with perinatal brain injury and 5 typically developing infants. Tractography was used to identify the corticospinal tract, a key motor pathway often affected by perinatal brain injury, and tract-based spatial statistics (TBSS) were used to examine broader white matter networks. Diffusion parameters from the diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) models were compared between infants with and without typical general movements. Results: Corticospinal tract integrity did not differ between groups when averaged across hemispheres. However, infants with asymmetric general movements exhibited greater corticospinal tract asymmetries. A subset of infants with atypical general movement trajectories at <6 weeks and 3–5 months of age showed reduced corticospinal tract integrity compared to those with typical general movements. TBSS revealed significant differences in white matter integrity between infants with typical and atypical general movements in several white matter pathways, including the corpus callosum, the right posterior corona radiata, bilateral posterior thalamic radiations, the left fornix/stria terminalis, and bilateral tapetum. Conclusions: These findings support and expand upon previous research suggesting that white matter integrity across multiple brain regions plays a role in the formation of general movements. Corticospinal integrity alone was not strongly associated with general movements; interhemispheric and cortical-subcortical connectivity appear critical. These findings underscore the need for further research in larger, diverse populations to refine early biomarkers of neurodevelopmental impairment and guide targeted interventions. Full article

Background and Objectives: Zinc finger proteins are important transcription factors that regulate gene expression and play a critical role in neurodevelopment including autism spectrum disorders (ASDs). They are involved in a variety of cellular processes, including cell proliferation, differentiation, and apoptosis. Materials and Methods: Whole-exome sequencing (WES) analysis on a patient diagnosed with ASD. Results: Sequencing identified a homozygous insertion causing a stop codon, resulting in the removal of several functional domains including the zinc finger C2HC/C3H type of the ZC2HC1C protein. To date, no MIM entry has been assigned to the detected gene. In silico predictions described the variant as likely pathogenic, indicating an autosomal recessive inheritance pattern. In this study, we hypothesize that this homozygous mutation disrupts protein function and may represent a susceptibility gene for autism. The parents and the patient’s sister were healthy and carry the variant in the heterozygous condition. This gene is expressed in brain tissues showing high expression in both the choroid plexus (ChP) and midbrain, whose dysfunctions, as reported, may lead to ASD. Moreover, predictive pathway analyses indicated the probable involvement of this gene in primary cilia development. This process has been frequently linked to neurodevelopmental impairments, such as autism, as documented in previous studies. Conclusions: Further analyses are needed via in vitro functional assays or by ZC2HC1C gene knockout to validate its functional role. Full article

As novel pollutants, flame retardants (FRs) are prone to accumulating in soil and might increase human health risks. It is advisable to emphasize the biomagnification of FRs within the terrestrial food chain, particularly concerning mammals occupying higher trophic levels. Exposure to soil particles laden with FRs may result in numerous health complications. These findings offer significant insights into FR pollutant profiles, tracing origins and recognizing health risks associated with soil samples. Reports have revealed that exposure to FRs can pose serious health risks, including neurodevelopmental impairments, endocrine system disruption, and an increased likelihood of cancer. Nanomaterials, with their high surface area and flexible properties, possess the ability to utilize light for catalytic reactions. This unique capability allows them to effectively degrade harmful contaminants, such as FRs, in soil. Additionally, biological degradation, driven by microorganisms, offers a sustainable method for breaking down these pollutants, providing an eco-friendly approach to soil remediation. These approaches, combined with optimum remediation strategies, hold great potential for effectively addressing soil contamination in the future. Further research should prioritize several key areas, including ecological behavior, contaminant monitoring, biological metabolomics, toxicity evaluation, and ecological impact assessment. Full article

Background/Objectives: Learning disabilities (LDs) are complex neurodevelopmental conditions influenced by genetic, epigenetic, and environmental factors. Recent research suggests that maternal autoimmune conditions, perinatal stress, and vitamin D deficiency may contribute to neuroinflammation, which, in turn, can disrupt brain development. Chronic neuroinflammation, driven by activated microglia and astrocytes, has been associated with synaptic dysfunction and cognitive impairment, potentially impacting learning and memory processes. This study aims to explore the relationship between neuroinflammation and LDs, emphasizing the role of electroencephalography (EEG) biomarkers in early diagnosis and intervention. Methods: A systematic analysis was conducted to examine the prevalence, core symptoms, and typical age of diagnosis of LDs. EEG biomarkers, particularly theta, gamma, and alpha power, were assessed as indicators of neuroinflammatory states. Additionally, artificial neural networks (ANNs) were employed to classify EEG patterns associated with LDs, evaluating their diagnostic accuracy. Results: Findings indicate that EEG biomarkers can serve as potential indicators of neuroinflammatory patterns in children with LDs. ANNs demonstrated high classification accuracy in distinguishing EEG signatures related to LDs, highlighting their potential as a diagnostic tool. Conclusions: EEG-based biomarkers, combined with machine learning approaches, offer a non-invasive and precise method for detecting neuroinflammatory patterns associated with LDs. This integrative approach advances precision medicine by enabling early diagnosis and targeted interventions for neurodevelopmental disorders. Further research is required to validate these findings and establish standardized diagnostic protocols. Full article

Background and Objectives: Theory of mind (ToM) deficits in children with ADHD are closely related to social difficulties and problems in interpersonal interactions. Evidence suggests that these cognitive deficits negatively affect the ability to understand and respond to others’ emotions and intentions, thus contributing to social isolation and a lower quality of life. However, the findings across studies vary, indicating that ADHD subtype and comorbidities, such as anxiety and mood disorders, can significantly influence sociocognitive deficits, modulating the extent of social problems. Materials and Methods: This review examines the relationship among ADHD, ToM, and empathy, analyzing studies comparing children with ADHD with peers with typical development or other neurodevelopmental conditions. A search in PubMed, Scopus, and the Cochrane Library prior to January 10, without time restrictions, using “ADHD”, “Cognitive Empathy”, and “Theory of Mind” identified relevant studies assessing these abilities through neuropsychological tests or questionnaires. Results: Of the initial 243 studies, 23 studies met the inclusion criteria. Children with ADHD exhibited significant impairments in ToM and empathy, affecting social cognition and interpersonal understanding. Various assessment tools revealed difficulties in understanding beliefs, emotions, and intentions, with executive function deficits playing a crucial role in shaping these social challenges. Conclusions: This review highlights the need for targeted therapeutic interventions that not only address cognitive deficits but consider emotional and metacognitive aspects, such as emotion regulation and self-awareness. Future research should focus on integrating executive function training with approaches that develop metacognitive and emotional skills, thus providing more comprehensive support. Full article

Background: Emerging evidence suggests that the maternal microbiome plays a crucial role in shaping fetal neurodevelopment, immune programming, and metabolic health. Dysbiosis during pregnancy—whether gastrointestinal, oral, or vaginal—can significantly influence pregnancy outcomes and long-term child health. Materials and Methods: The search was performed using databases such as PubMed, Scopus, and Google Scholar including research published from January 2000 to January 2025. The keywords used were “Fetal Programming”, “ Maternal Immune Activation”, “Maternal microbiome”, “Microbiota–Gut–Brain Axis”, and “Pregnancy Dysbiosis”. Results: The maternal microbiome undergoes substantial changes during pregnancy, with alterations in microbial diversity and function linked to conditions such as gestational diabetes, obesity, and preeclampsia. Pregnancy-related dysbiosis has been associated with adverse neurodevelopmental outcomes, including an increased risk of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and cognitive impairments in offspring. Conclusions: Understanding the intricate relationship between maternal microbiota and fetal health is essential for developing targeted interventions. Personalized microbiome-based strategies, including dietary modifications and probiotic supplementation, hold promise in optimizing pregnancy outcomes and promoting health in offspring. Full article

According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), neurodevelopmental disorders (NDDs) are a group of conditions that arise early in development and are characterized by deficits in personal, social, academic, or occupational functioning. These disorders frequently co-occur and include conditions such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Mood disorders (MDs), such as major depressive disorder and bipolar disorder, also pose significant global health challenges due to their high prevalence and substantial impact on quality of life. Emerging evidence highlights overlapping neurobiological mechanisms between NDDs and MDs, including shared genetic susceptibilities, neurotransmitter dysregulation (e.g., dopaminergic and serotonergic pathways), neuroinflammation, and hypothalamic–pituitary–adrenal (HPA) axis dysfunction. Environmental factors such as early-life adversity further exacerbate these vulnerabilities, contributing to the complexity of their clinical presentation and comorbidity. Functional neuroimaging studies reveal altered connectivity in brain regions critical for emotional regulation and executive function, such as the prefrontal cortex and amygdala, across these disorders. Despite these advances, integrative diagnostic frameworks and targeted therapeutic strategies remain underexplored, limiting effective intervention. This review synthesizes current knowledge on the shared neurobiological underpinnings of NDDs and MDs, emphasizing the need for multidisciplinary research, including genetic, pharmacological, and psychological approaches, for unified diagnosis and treatment. Addressing these intersections can improve clinical outcomes and enhance the quality of life for individuals affected by these disorders. Full article