Search Results (256)

Background/Objectives: Children’s mental health and positive development are shaped by family, environmental, and individual factors. Although neurodevelopmental disabilities (NDDs) are well-established correlates of poorer mental health outcomes, few national-scale studies have simultaneously modeled positive (flourishing) and negative (anxiety, depression) outcomes within a unified ecological framework. This study examined how parent mental health, peer victimization, neighborhood and school context, and four NDD diagnoses (autism spectrum disorder [ASD], attention-deficit/hyperactivity disorder [ADHD], developmental delay, and learning disability) are associated with flourishing, current anxiety, and current depression in a national sample of U.S. children aged 6–17 years. Methods: Cross-sectional data from the 2023–2024 National Survey of Children’s Health (NSCH; N = 71,172) restricted to ages 6–17 with complete data (unweighted n = 64,263; weighted population estimate ≈ 44.6 million children) were analyzed using Complex Sample logistic regression (SPSS 30), accounting for stratified design (state × stratum), household clustering, and sampling weights. Three hierarchical models were estimated for each outcome. NDD-stratified subgroup analyses (n = 13,971; weighted ≈ 8.6 million) triangulated moderation findings. Multiple imputation (m = 5) sensitivity analyses confirmed robustness. Results: Weighted prevalence was 60.7% for flourishing, 13.2% for current anxiety, and 5.1% for current depression. In Block 2 models, poorer parent mental health and more frequent bullying victimization were robustly associated with all outcomes (flourishing OR = 0.62 and 0.65; anxiety OR = 1.64 and 1.63; depression OR = 1.95 and 1.75; all p < 0.001). Supportive neighborhood (flourishing OR = 1.40, depression OR = 0.80) and safe school (flourishing OR = 1.20, anxiety OR = 0.87) were protective. ADHD was the strongest disability-specific correlate (flourishing OR = 0.29; anxiety OR = 4.69; depression OR = 4.27). Three of the twelve interaction terms were significant, all involving ADHD. Relative to children without any NDD, subgroup analyses suggested attenuated associations of parent mental health and bullying with anxiety and depression among children with any NDD (e.g., bullying on anxiety: no-NDD aOR = 1.73 vs. Any-NDD 1.52); however, formal interaction tests identified ADHD as the only significant moderator of these associations. On the absolute-risk scale, however, the increase in internalizing problems with more frequent bullying was larger in children with ADHD. Conclusions: Family mental health support and bullying prevention are universally relevant levers for improving children’s mental health and flourishing. Although attenuation of the odds-ratio associations was observed primarily in ADHD-related analyses, specifically for the internalizing outcomes (anxiety and depression), universal anti-bullying and parent mental health interventions remain relevant for children with NDDs, supporting integration into pediatric clinical and public-health programs alongside disability-specific support pathways. Full article

Background/Objectives: Tourette syndrome and other chronic tic disorders are neurodevelopmental conditions characterized by intermittent motor/phonic tics and frequent behavioral comorbidity. Poor sleep quality is often reported by patients with tic disorders; however, little is known about the prevalence and clinical correlates of disruption in sleep physiology. Methods: We conducted a systematic literature review of clinical studies evaluating sleep using at least one validated sleep outcome (questionnaire, polysomnography, or coded clinical diagnosis). Results: Despite high heterogeneity in age ranges, diagnostic formulations, outcome measures, and confounder handling, converging evidence across designs indicated a significantly higher prevalence of sleep disturbance in patients with Tourette syndrome and other chronic tic disorders compared to controls. Specifically, registries showed significantly greater insomnia rates (aOR 6–7); case–control studies revealed a 9-fold increase in night-waking, bedtime resistance, parasomnias, and daytime drowsiness; polysomnography studies demonstrated sleep fragmentation, with decreased efficiency, longer latency, and more awakenings. Conclusions: Sleep disorders are relatively common in patients with Tourette syndrome and other chronic tic disorders, with clinical implications for both arousal instability and sleep initiation/maintenance issues. Further research is needed to better understand the complex interplay between altered sleep patterns and tic expression, as well as the impact of behavioral comorbidities. Our findings highlight a need for personalized treatment interventions focusing on sleep problems in the context of tic disorders. Full article

Background/Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental disease with both clinical and genetic heterogeneity. Several loss-of-function variants in the chromodomain helicase DNA-binding protein 8 (CHD8) gene have been identified in individuals with ASD and/or developmental delay/intellectual disability. These are associated with specific clinical manifestations, including overgrowth, macrocephaly, sleep disturbance, and gastrointestinal problems. Methods: We performed clinical exome sequencing in a female patient with ASD and macrocephaly. RNA analysis from peripheral blood was carried out to investigate the functional effect of the identified variants. Results: We identified a novel maternally inherited CHD8 variant (c.5390+2T>C). Transcript analysis demonstrated that this variant disrupts the canonical splice donor in intron 30, causing splicing anomalies in the CHD7-binding domain of the CHD8 protein, resulting in a truncated inactive protein. Conclusions: In conclusion, this study identified a novel splice-site variant in the CHD8 gene with experimentally confirmed pathogenic effects on RNA splicing, expanding the mutational spectrum of CHD8-related neurodevelopmental disorders. The considerable intrafamilial phenotypic variability associated with CHD8 haploinsufficiency supports the presence of reduced penetrance and highlights the influence of modifying factors on the clinical expression of CHD8-related disorders. Full article

Background: Attention-Deficit Hyperactivity Disorder (ADHD) is a complex neurodevelopmental disorder affecting executive functions such as impulse control, focus, and organization. This study addresses three research questions: current models and gaps in ADHD interventions, ways to enhance strengths and address weaknesses, and program recommendations for various ages. The aim is to develop a comprehensive framework to improve ADHD interventions, with a particular focus on youth and addressing existing gaps to enhance effectiveness. Methods: The current study systematically reviews the literature to answer these research questions. Sources were examined to identify existing intervention models, documented strengths and weaknesses, and recommendations relevant to different developmental stages. Results: Findings show that interventions for ADHD are varied and include psychological or behavioural therapy, family-school issues and parent involvement, school-based approaches, and medication. Key challenges include a lack of evidence-based practices, gaps in translational research, and insufficient teacher training. Notable strengths are family-school conference and family input, though there is less emphasis on building problem-solving capacity and family agency. Conclusions: Program recommendations highlighted in the literature include the need for family involvement, matching intervention intensity to individual needs, and ensuring professional education for special education. Addressing these gaps is essential for strengthening ADHD interventions and improving outcomes for children and youth. Full article

β-thalassemia minor, often referred to as the β-thalassemia trait, is among the most prevalent hemoglobinopathies globally, impacting around 80–90 million carriers, with a prevalence of up to 15% among Mediterranean, Middle Eastern, and Asian populations. Although traditionally regarded as clinically benign, pregnancy imposes hematologic and metabolic stressors that may unmask latent vulnerabilities. This review combines the latest data and findings about the pathophysiology of β-thalassemia minor during pregnancy, its short-term outcomes on the mother and fetus, and its long-term impact on the child, as well as management techniques. A narrative review of PubMed-indexed studies (2000–2025) was conducted, including cohort and case–control studies, systematic reviews, meta-analyses, and international guidelines. Outcomes were organized by theme, and quantitative findings (prevalence, relative risks, odds ratios) were combined when available. Anemia is a common health issue for mothers. Literature mentions that the pooled incidence is between 30% and 40% during the third trimester, with ~5%of carriers needing a blood transfusion (mainly in iron-deficient or baseline Hb 6–8 g/dL cases). Meta-analyses have shown elevated risks of pre-eclampsia (odds ratio (OR) ~ 1.4, 95% confidence interval (CI) 1.1–1.8) and postpartum hemorrhage (PPH); however, estimates differ by region. The odds of preterm delivery (OR ~ 1.4), small-for-gestational-age (SGA) (OR ~ 1.5), and low birth weight (LBW) are slightly increased for carriers, and neonatal intensive care unit (NICU) admission rates are also higher for carriers. However, the risk of stillbirth is not always increased. The usual approach is iron supplementation guided by ferritin levels to prevent overload, personalized transfusion thresholds, and regular folate support. There is not much evidence for long-term consequences for children of carrier mothers since no research has followed more than 200 children born to carrier mothers into adulthood. However, maternal anemia is linked to slower growth, neurodevelopmental issues, and a higher risk of cardiometabolic problems in larger groups of pregnant women. However, maternal anemia is associated with slower growth, neurodevelopment, and higher cardiometabolic risk in larger groups of pregnant women. β-thalassemia minor during pregnancy usually has a mild, though significant, impact. While most pregnancies proceed without complications, this condition is associated with a significantly higher prevalence of anemia and other adverse postnatal outcomes. Consequently, the implementation of risk-stratified monitoring, smart supplementation, and standardized management protocols is essential. Prospective registries, mechanistic placental research, and long-term offspring cohorts are necessary to better understand long-term trends. Full article

Brain organoids represent three-dimensional structures that allow for human-specific studies in brain development, pathology and therapeutics. These self-organizing systems, formed through the differentiation of human pluripotent stem cells, can mimic important cellular and molecular events of brain development and therefore serve as a platform for the investigation of neurodevelopmental and neurodegenerative diseases, brain injuries, and tumorigenesis. Although brain organoids show promising perspectives in the study of human physiology, existing brain organoid platforms are hindered by issues of under vascularization, immaturity and protocol variability. Nevertheless, the rapid development of new bioengineering, microfluidic and multi-omics tools and approaches allows us to overcome existing problems and increase the physiological significance of these organoids. Brain organoid transplantation and functional studies further enhance the applications of brain organoids in drug screening, disease modeling and personalized medicine. Here, we provide an overview of recent developments in the field of brain organoid cultures, functional characteristics and translational applications. Full article

Impulsivity is a core transdiagnostic construct in adolescent psychiatry, associated with emotional dysregulation, behavioral disorders, and increased vulnerability to mental health problems. Adolescents engaged in performing arts education may experience heightened psychosocial stressors that challenge self-regulatory capacities during a critical neurodevelopmental period. Methods: This mixed-methods study examined psychosocial and family-related factors associated with impulsivity in adolescent students enrolled in drama programs. Two focus groups with 28 upper-grade students (grades 11–12) explored subjective experiences of stress, emotional overload, and family communication. Based on these findings, a 77-item questionnaire was developed and administered to 90 ninth-grade students. Impulsivity was assessed using the Barratt Impulsiveness Scale (BIS). Results: An exploratory stepwise multiple linear regression analysis identified perceived school-related stress (β = 0.370, p < 0.001), conflictual parental communication (β = 0.273, p = 0.013), and discomfort during school discussions at home (β = 0.331, p < 0.001) as significant predictors of higher impulsivity scores. Conclusions: The findings highlight the interaction between neurodevelopmental vulnerability and environmental stressors in shaping impulsivity during adolescence. These results are clinically relevant for child and adolescent psychiatry, emphasizing the importance of early psychosocial interventions targeting stress regulation and family communication to prevent the escalation of impulsivity-related psychopathology. Full article

Background: Neurodegenerative diseases are a major health problem, and the neuropsychiatric symptoms seen in these diseases adversely impact the lives of patients, families, and caregivers. Inappropriate aggressive behavior is a highly disruptive symptom and a leading cause of institutionalization. There are no approved drugs specifically for the treatment of problematic aggression, and the off-label use of antipsychotics has limited benefit with significant side effects and safety risks. This review discusses dysregulated arginine vasopressin (AVP) signaling in fear–threat circuitry as a key driver of inappropriate aggression. Because the AVP 1a receptor (V1aR) is the dominant subtype in the CNS, the selective antagonism of this receptor represents a well-rationalized target for the treatment of aggression across neurodegenerative, psychiatric, and neurodevelopmental disorders. Objectives: Our goal was to summarize the basis for using V1aR antagonists as a treatment for irritability and aggressive behavior. We describe its discovery, biosynthesis, receptor pharmacology, and CNS distribution, emphasizing V1aR localization in central fear–threat circuits. Translational evidence from animal studies, pharmacological neuroimaging, and lesion network mapping is presented. These data support the suggestion that heightened vasopressinergic tone biases socioemotional information processing toward negative valence, increasing threat sensitivity and the likelihood of inappropriate aggressive responses. Emerging clinical data support this framework. Highly selective, CNS-penetrant V1aR antagonists reduced aggressive behavior and had an excellent safety profile in phase 2 studies in Huntington’s disease and intermittent explosive disorder, with efficacy signals across caregiver-reported, clinician-rated, and incident-based measures. Furthermore, pharmacological neuroimaging showed that V1aR antagonism normalizes AVP-induced alterations in activity within fear–threat circuitry. Conclusions and Future Directions: Preclinical, translational, and clinical findings to date support V1aR antagonism as a promising strategy for treating pathological aggression across disorders. Additional experimental medicine studies and clinical trials are needed to conclusively establish efficacy in various disease populations, and we note the need for improved trial designs and analytical methods as part of the development process. Full article

The aim of this study was to assess long-term outcomes in patients with different vascular types of childhood stroke. Methods: Data for children with childhood stroke (aged 29 days to 18 years) were collected from the Estonian Pediatric Stroke Database. Outcomes (death, recurrent stroke, epilepsy, neurodevelopmental outcome by pediatric stroke outcome measure (PSOM)) were assessed at a minimum of two years after stroke. Results: Long-term outcome data were available for 44 patients with childhood stroke (including three patients who died of stroke). According to the PSOM, based on gender, age, location of stroke and epilepsy, there were no differences in outcomes, but patients with a Pediatric NIH Stroke Scale (PedNIHSS) score of ≥6 had worse outcomes compared to patients with a score of <6. Children with arterial hemorrhagic stroke (AHS) were more likely to die, suffer from epilepsy and develop problems in the cognition/behavior PSOM subscale compared to children with arterial ischemic stroke (AIS). Combined poor outcomes (epilepsy, PSOM ≥ 1, recurrent stroke, mortality) occurred in 75% (33/44) of all patients with long-term outcome data. Conclusions: Combined poor outcomes occurred in 75% of the patients with childhood stroke. Patients with AHS showed higher mortality and worse long-term outcomes compared to patients with AIS in certain neurodevelopmental domains. Full article

Objective: Copy number variants (CNVs) overlapping genes associated with neurodevelopmental disorders in patients with epilepsy are particularly concentrated in epilepsy hotspot loci. The aim of this study was to evaluate epilepsy as a component of the dysmorphic–neurodevelopmental phenotype in patients with recurrent CNVs. Methods: The study included genetic and clinical data from 177 pediatric patients carrying 17 recurrent CNVs showing well-documented enrichment in epilepsy or associated with genetic OMIM syndromes. Results: Epilepsy was diagnosed in 50 of 177 children (28.2%), developmental delay in 147 (83.0%), dysmorphic features in 104 (58.8%), behavioral problems in 62 (35.0%), and congenital anomalies in 55 (31.1%). Among recurrent CNV hotspots, the del16p11.2 BP4–BP5 deletion was the most frequent, occurring in 39 of 177 patients. Ten children (25.6%) with del16p11.2 presented with epilepsy as part of the phenotype. Other frequently represented CNVs included del15q11.2 BP1–BP2 (OMIM #615656; 19/177 patients, 4/19 with epilepsy), del1q21.1 (OMIM #612474; 15/177, 6/15 with epilepsy), del15q13.3 (OMIM #612001; 13/177, 4/13 with epilepsy), and dup16p11.2 (OMIM #614671; 12/177, 1/12 with epilepsy). The highest proportion of epilepsy as a phenotypic component was observed in patients with del1p36 (OMIM #607872; 6/9 patients) and del1q21.1 (OMIM #612474; 6/15 patients). Conclusions: Our data support the clinical utility of CNV testing in patients with epilepsy accompanied by additional neurodevelopmental or dysmorphic features, in line with current diagnostic guidelines. The epilepsy-plus phenotype may help clinicians identify patients who are most likely to benefit from CNV analysis. Full article

We report a thirty-six-year-old woman with intellectual disability who was referred for evaluation of suspected obstructive sleep apnea. The initial clinical impression suggested a syndromic case, so comprehensive genetic testing was undertaken. Overnight polysomnography revealed a severe rapid eye movement–predominant obstructive sleep apnea syndrome with an apnea–hypopnea index of 31.9 events per hour, rapid eye movement apnea–hypopnea index of 113.8 events per hour, and lowest oxygen saturation of 66%. Treatment with continuous positive airway pressure improved respiratory and sleep quality indices and was well tolerated. Whole-exome sequencing identified a de novo splice site variant in the pleckstrin homology domain interacting protein gene (c.41-1G > A), confirming a molecular diagnosis of Chung–Jansen Syndrome. Chung–Jansen syndrome is a rare neurodevelopmental disorder caused by heterozygous pathogenic variants in the pleckstrin homology domain interacting protein gene, marked by developmental delay, intellectual disability, behavioral abnormalities, dysmorphism, and progressive obesity. PHIP influences central and peripheral pathways controlling satiety, pancreatic function, and body weight. Despite frequent reports of sleep problems, systematic evaluation of sleep-disordered breathing has been limited. This adult case provides the first polysomnographic confirmation in the syndrome, supporting proactive screening for obstructive sleep apnea—especially in those with obesity. Integrating genetic assessment into sleep care can reduce diagnostic delays and better guide therapy and prognosis. Full article

Tourette Syndrome (TS) is a neurodevelopmental disorder depicted by the occurrence of tics and accompanying behavioral problems that commonly appear during childhood. Tics, both motor and vocal, may cause musculoskeletal pain. Both acute and chronic muscle pain have been recognized as a common comorbid aspect of TS-related tic disorders in childhood. The pain most reported in children includes cervical, throat, shoulder, ocular, and joint pain, with most children reporting musculoskeletal pain in more than one part of the body. The impact of muscular pain caused by motor and phonic tics can negatively affect a child’s quality of life. This review describes the association and causation of musculoskeletal pain in childhood tics and TS, which are commonly under recognized and diagnosed. An analysis of the presence of musculoskeletal pain, the severity of the pain, the location of the pain and the movement incapacity due to pain in children is reviewed. Pharmacological and non-pharmacological interventions known to improve musculoskeletal pain in children are highlighted with supportive frameworks evaluated. Further research is needed to better understand musculoskeletal pain cause(s) and prevalence along with age-appropriate assessment methods and outcomes measures. Motor- and phonic-related musculoskeletal pain should be recognized as a common comorbid characteristics of TS and tic disorders in childhood. Such recognition may lead to greater therapeutic opportunities for this problematic condition. Full article

Background/Objectives: The foetal alcohol syndrome spectrum is linked with neurodevelopmental delay and cognitive and educational problems. Direct consequences of prenatal alcohol exposure include impaired processes of neural migration and brain development. Among the important features present in affected children are impaired communicational skills and intelligence. Methods: Here we presented the case–control comparison of 124 children with foetal alcohol syndrome spectrum disorder (FAS: 62 (50%), pFAS: 34 (27.42%) and ARND: 28 (22.58%)) and 53 healthy controls regarding intelligence quotient and a verbal fluency task. The verbal and non-verbal intelligence was measured using the WISC-R scale, and the verbal fluency task encompassed phonemic, semantic and categorial assessment in 15 and 60 s; we used the authors’ parental/caregiver survey to determine risk factors. In statistical analysis both methods of classical parametric/non-parametric tests and machine learning algorithms were used. Results: Foetal alcohol syndrome spectrum patients were clearly distinguished from healthy controls regarding total verbal and non-verbal intelligence, as well as all three categories of verbal fluency (p < 0.01). ML methods distinguished an FAS group with 0.49 precision and 80% recall and for pFAS and ARND diagnoses we obtained: 0.50/0.33 precision and 3%/7% recall. None of the parameters analysed in our study differentiated foetal alcohol syndrome, partial foetal alcohol syndrome and alcohol-related neurodevelopmental disorders. Conclusions: Children with foetal alcohol syndrome spectrum disorder markedly differ from healthy control subjects in intelligence and verbal fluency. The diagnostic sub-types of foetal alcohol spectrum are not clearly defined in obtained neuropsychological and clinical data. Full article

22q11.2 deletion syndrome (22q11.2DS) is the most common recurrent microdeletion in humans and a prototypical high-risk neurogenetic copy number variant (CNV) associated with a broad spectrum of neurodevelopmental and psychiatric disorders, including intellectual disability (ID), autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), anxiety, and psychotic symptoms. This hemizygous deletion encompasses multiple genes involved in brain development and neural circuit function, contributing to marked phenotypic variability and multisystem involvement. In pediatric populations, deficits in adaptive functioning are frequently reported and may occur independently of global intellectual impairment, reflecting broader behavioral vulnerabilities within this genetic risk architecture. Background/Objectives: This study aimed to characterize the sociodemographic, clinical, and intellectual profiles of children and adolescents with 22q11.2DS and to examine adaptive functioning and its associations with behavioral difficulties. Methods: Thirty-four patients aged 1–17 years with a confirmed molecular diagnosis of 22q11.2DS were assessed. Standardized instruments were used to evaluate cognitive performance, adaptive functioning, and behavioral outcomes. Results: Intellectual disability was highly prevalent, with most participants showing combined cognitive and adaptive impairments. Adaptive functioning was compromised across domains, with relatively higher socialization scores compared to other areas, such as daily living skills. Multivariate analyses indicated associations between sociodemographic factors and behavioral difficulties, as well as between social problems and lower global adaptive functioning. Conclusions: Together, these findings contribute to the characterization of the adaptive and behavioral phenotype associated with a high-risk neurogenetic CNV and highlight the relevance of adaptive functioning as a key outcome for early evaluation and intervention in pediatric 22q11.2DS. Full article

Background: The COVID-19 virus is a source of both acute and chronic stress for many people. This stress could uniquely impact children and their mental health. Research has shown that children with neurodevelopmental disorders such as Attention-Deficit/Hyperactivity Disorder (ADHD) are at an increased risk of negative mental health symptoms due to stress, but high-quality sleep may be associated with a protective role against these symptoms. We, therefore, aimed to investigate whether the impacts of COVID-19 and sleep problems were independently linked with children’s mental health and to examine whether sleep could mediate the relationship between COVID-19 impact and child mental health. Finally, we sought to compare the degree to which sleep problems could mediate this relationship in children without ADHD and in children with ADHD. Methods: In this cross-sectional study, a total of 304 parents of children were sampled from a larger study investigating the impact of the COVID-19 pandemic on Canadian families and children in the spring of 2021. Parents reported on their children’s mental health, sleep, and the impacts of COVID-19 on their child. Of the total sample, 234 children were reported as having an ADHD diagnosis, and 70 children were reported to not have ADHD. Results: We found that both the impact of COVID-19 and sleep problems independently and positively contributed to the mental health symptoms (p < 0.001) experienced by children with ADHD and without ADHD. Children with ADHD were found to have higher scores for COVID-19 child impact, sleep problems, and negative mental health. However, sleep problems had a greater impact on the mental health of children without ADHD compared to ADHD children. Additionally, the results suggest that sleep problems mediated ~20% of the relationship between COVID-19 impact and child mental health in children with ADHD and ~51% of this relationship in children without ADHD. Conclusions: The findings emphasize the significant role of sleep in mediating child mental health symptoms during periods of stress in children without ADHD and in children with ADHD. We highlight the importance of considering sleep quality and supporting healthy sleep in times of stress to improve child mental health symptoms. Full article