Search Results (313)

Characterized by social communication deficits and the presence of restricted and repetitive behaviors, autism spectrum disorder (ASD) is a significant neurodevelopmental condition. Genetic studies have revealed a strong association between ASD and numerous mutations that alter the function of key proteins, either through activation or inactivation. These alterations are widely hypothesized to affect neuronal morphogenesis; however, a comprehensive understanding of the specific molecular cascades driving these cellular and symptomatic changes remains lacking. In this study, we report for the first time that signaling through the atypical Rho family guanine-nucleotide exchange factor (GEF) Dock7 and ErbB2, an activator acting upstream of Dock7, drives the excessive elongation of neuronal processes observed in association with the ASD- and intellectual disability (ID)-linked semaphorin-5A (Sema5A) Arg676Cys variant (p.Arg676Cys). Knockdown of Dock7 using short hairpin RNA or inhibition of ErbB2 kinase signaling with a specific chemical inhibitor reduced this excessive process elongation in primary cortical neurons. Similar results were obtained in the N1E-115 cell line, a neuronal cell model that undergoes neuronal morphological differentiation. Moreover, inhibition of ErbB2-Dock7 signaling specifically decreased the overactivation of the downstream molecules Rac1 and Cdc42. These findings indicate that the ErbB2–Dock7 signaling axis plays a role in mediating the aberrant neuronal morphology associated with the ASD- and ID-linked Sema5A p.Arg676Cys. Targeting this pathway may therefore offer a potential approach to addressing the molecular and cellular developmental challenges observed in ASD. Full article

Background: Childhood cancer survivors (CCSs) are at heightened risk of long-term neurocognitive and emotional difficulties that can affect educational attainment, social participation, and overall quality of life. These outcomes vary across developmental stages and are influenced by treatment modality, age at diagnosis, and central nervous system (CNS) involvement. Methods: A comprehensive literature search was conducted in PubMed, Scopus, PsycINFO, and Web of Science for articles published between January 2000 and June 2024. Search terms included combinations of “childhood cancer survivors,” “neurocognitive outcomes,” “executive function,” “emotional regulation,” and related MeSH terms. Inclusion criteria required peer-reviewed studies assessing CCS using standardized neuropsychological or emotional measures. Results: Evidence indicates persistent deficits in processing speed, working memory, and higher-order executive functions, with additional challenges in attention and memory. Emotional difficulties, including anxiety, depression, and social withdrawal, were prevalent and often co-occurred with cognitive impairments. Developmental timing of cancer and treatment was a key determinant of outcome. Family functioning, school reintegration support, and broader social environments emerged as important moderators of resilience. Conclusions: CCSs face complex, interrelated cognitive and emotional challenges that warrant early identification and ongoing, developmentally tailored intervention. Integrated approaches combining cognitive remediation and psychosocial support appear most effective. Future research should prioritize longitudinal designs, multi-informant assessments, and culturally sensitive frameworks to inform targeted prevention and rehabilitation strategies. Our synthesis highlights that deficits in processing speed and working memory are most pronounced following CNS-directed therapies during early developmental stages, whereas emotional vulnerabilities such as anxiety and social withdrawal often emerge later in adolescence. Interventions combining cognitive remediation, targeted psychosocial support, and structured school reintegration show the strongest evidence for improving adaptive outcomes. Coordinated survivorship care across healthcare, educational, and family systems is essential to sustain developmental recovery. Full article

Background: Dementia is a common disease in the elderly, and its prevalence continues to increase worldwide. A significant proportion of patients with dementia are hospitalised due to comorbidities. Health-related quality of life (HRQoL) reflects overall health and is used in clinical trials, economic evaluations, and population health studies. The aim of this study was to assess the risk of dementia and quality of life related to the health status of patients hospitalised in geriatric wards. Methods: The study was conducted in geriatric wards of hospitals in the Lublin region. A total of 308 patients aged 65–98 years participated in the study. Results: The NOSGER scale evaluation of patients was at the average level of 75.82 points. The seniors showed best functioning in the area of disruptive behaviours (average 9.45 points), and the greatest deficits were found in the area of instrumental activities of everyday life (15.95 points). The cohort of patients assessed their overall quality of life at the average level of 3.16 ± 0.78 points and health status at 2.44 ± 0.77 points. The highest scores were given to the social domain (59.52 ± 13.69) and the environmental domain (56.96 ± 1.95). Conclusions. Psychophysical fitness was shown to decline in correlation with geriatric ward patients’ quality of life self-assessment. Full article

Background: The ongoing discourse surrounding the connection between atrial fibrillation (AF) and stroke continues to be a topic of considerable discussion. Atrial fibrillation (AF) is a well-established risk factor for ischemic stroke, yet the prognostic significance of paroxysmal AF in functional recovery remains uncertain. While persistent AF has consistently been associated with more severe strokes and poorer outcomes, evidence regarding paroxysmal AF is limited and conflicting. This research examines how paroxysmal AF influences the severity of post-stroke disability in individuals experiencing acute ischemic stroke. Materials and Methods: A total of 236 patients presenting with acute ischemic stroke and cardiovascular risk factors were evaluated upon admission to the Neurology Department. Of these, 118 patients with paroxysmal AF were assigned to Group A, and 118 patients without AF were assigned to Group B. To determine the severity of disability, clinical, neurological, and imaging assessments were performed utilizing the modified Rankin Scale (mRS), Activities of Daily Living (ADL) score, National Institutes of Health Stroke Scale (NIHSS), and Medical Research Council (MRC) scale. Results: Patients in Group A exhibited significantly poorer outcomes in comparison to those in Group B, evidenced by lower ADL scores, elevated NIHSS and MRC scores, and increased levels of disability (p < 0.05). Within Group A, a stronger correlation was observed between mRS scores and neurological symptoms, motor deficits, and daily functioning. Logistic regression analysis indicated that among all stroke patients (comprising Groups A and B), the probability of experiencing moderate to severe disability (mRS ≥ 3) escalated by 31.6% for each unit increase in NIHSS and diminished by 64.5% for every unit increase in MRC. In Group A, an increase of one unit in ADL correspondingly lowered the risk of mRS ≥ 3 by 22.7%, in contrast to a reduction of 17.8% in the overall stroke population (Groups A and B combined). Additionally, an enhancement in MRC score led to an 83.5% decrease in the risk of disability within Group A, compared to a 75.8% reduction in Group B. Moreover, in Group A, each unit increment in the HAS-BLED score was associated with a 32.5% rise in the risk of severe disability (OR = 1.325; 95% CI: 1.015–1.729; p < 0.05). Conclusions: Paroxysmal atrial fibrillation was significantly associated with a higher risk of moderate to severe disability following acute ischemic stroke compared to patients without AF. The severity of post-stroke disability in Group A is closely linked to reduced functional independence (lower ADL), more pronounced neurological impairment (higher NIHSS), greater motor deficits (lower MRC), and increased bleeding risk (higher HAS-BLED score). These findings highlight the importance of early identification and comprehensive monitoring of functional, neurological, and cardiovascular parameters in stroke patients with paroxysmal AF. Tailored rehabilitation strategies aimed at improving motor function, daily living activities, and controlling hemorrhagic risk can play a crucial role in reducing long-term disability and enhancing the reintegration of these patients into family and social life. Full article

Background/Objectives: This study examines the impact of long-term institutionalization on the linguistic and communicative abilities of people diagnosed with schizophrenia, focusing on the influence of educational background. Schizophrenia is characterized by cognitive and social deficits, including disruptions to language use and communicative engagement. Prolonged institutionalization can exacerbate these impairments by depriving individuals of essential social interactions and cognitive stimulation. Methods: A case series approach was employed with 18 participants, and validated assessment tools such as the Montreal Evaluation of Communication and the Boston Diagnostic Aphasia Test were used to measure communicative performance. Results: Participants with higher educational attainment (nine or more years of schooling) who had been institutionalized for ten years or more exhibited significantly better performance than their less-educated counterparts across various communication domains, including comprehension of linguistic prosody, lexical fluency, and auditory comprehension. This implies that completing a higher degree may mitigate the cognitive decline impact of prolonged stays in an institution. However, the study design does not allow us to ascertain whether education functions as a mitigating factor. Conclusions: The results highlight the importance of incorporating educational considerations into therapeutic strategies for individuals with schizophrenia, especially those experiencing long-term institutionalization. Providing enhanced educational opportunities within institutional settings could mitigate the adverse effects of prolonged confinement and foster improved communication and social skills. These findings are consistent with research on cognitive reserve, which suggests that education fosters adaptive strategies and the utilization of alternative neural pathways. This enables individuals to maintain communication skills despite the cognitive impairment associated with schizophrenia. Full article

Autism spectrum disorder (ASD) is a complex, heterogenous, and prevalent neurodevelopmental disorder characterized by core symptoms, including social communication deficits, restrictive interests, and repetitive behaviors. Although environmental factors contribute to the etiology of ASD, the disorder has a strong genetic basis, although the specific genes involved in causing or contributing to the disorder remain to be conclusively identified. Whereas previous studies have focused on the cerebral cortex, hippocampus, and associated brain regions to uncover the underpinnings of ASD, emerging evidence indicates that dysfunction of the cerebellum is one of the most consistent associates of ASD. Traditionally thought to function solely in motor control, more recent studies have established that projections from the cerebellum make mono- and polysynaptic connections to a variety of non-motor areas including the cerebral cortex, hypothalamus, and hippocampus, and is involved in a range of cognitive, sensory, and behavioral functions. While several reviews of the molecular underpinnings of ASD have focused on the other brain regions, primarily the cortex, in this review we describe the key role that the cerebellum plays in the development of ASD and then focus on genetic variations that cause ASD, focusing on genes expressed and studied in the cerebellum. We have divided the ASD-associated genes in two subgroups—those that have been identified through a candidate gene approach with knowledge of their function in the cerebellum and their relationship to ASD subsequently confirmed in experimental models, and those identified through unbiased genetic analyses of individuals with ASD, many of which have not yet been characterized extensively and/or not studied in animal models. We also provide recently reported information on non-genetic factors that combine with genetic factors to promote ASD. Together, we hope our review will provide information on recent and significant findings related to the cerebellar underpinnings in ASD. Full article

Background/Objectives: Attention-deficit/hyperactivity disorder (ADHD) is increasingly recognized for its impact on social functioning, including deficits in social cognition and empathy. Emerging neurobiological evidence highlights the potential role of oxytocin in these impairments. However, the influence of pharmacotherapy, particularly methylphenidate (MPH) and atomoxetine (ATX), on these domains remains underexplored. This study aimed to examine the effects of MPH and ATX on social cognition, empathy, and serum oxytocin levels in children with ADHD. Methods: This study included 152 children aged 6–12 years diagnosed solely with ADHD. The patient group consisted of 102 children, comprising n = 52 receiving MPH and n = 50 receiving ATX for at least 3 months. The control group comprised 50 newly diagnosed, untreated children. A sociodemographic form, the Social Skills Rating Scale (SRSS), the Reading the Mind in the Eyes Test (RMET), the Bryant Empathy Index (BEI), and the Swanson, Nolan, and Pelham Questionnaire (SNAP-IV) were applied. Serum oxytocin levels were measured via venous blood samples. Results: Medicated children exhibited significantly elevated SRSS scores, irrespective of the pharmacotherapy administered. RMET scores were significantly higher in the ATX group. No significant differences were found between the three groups in terms of empathy scores and serum oxytocin levels. A significant negative correlation was identified between ADHD symptom severity and RMET and SRSS-Total scores. Regular medication use was a significant predictor of SRSS scores, while empathy and serum oxytocin levels were nonsignificant predictors. Conclusions: Pharmacotherapy may enhance social cognition among children with ADHD. Longitudinal studies are warranted to assess the long-term effects of medication on social cognition and empathy. Full article

The main characteristics of attention deficit hyperactivity disorder (ADHD) are associated with inattention, impulsivity, and/or hyperactivity. Those diagnosed with this neurodevelopmental disorder present with executive function and motor difficulties, which have repercussions in educational, occupational, or social areas. On the other hand, it has been evidenced that the regular practice of physical activity or exercise or sport could produce improvements in areas with difficulties. It is for this reason that the objective of the present review was to describe and analyze the effects of the practice of physical activity, exercise, or sport on executive functions in adults diagnosed with ADHD through the scientific literature (registry: INPLASY202530105). The articles indexed in PubMed (1145), Scopus (43), and WoS (2910) were searched using the following keywords: “Adult” OR “Adults” AND “Attention-Deficit/Hyperactivity Disorder” OR “Attention-Deficit with Hyperactivity Disorder” AND “Physical activity” OR “Exercise” OR “Sports” OR “Sport” AND “Executive Function”. In addition, four articles were identified using other search engines. A total of 10 articles met the selection criteria. TESTEX was used to assess the quality of the articles, and TIDierR was used to report the results. Of the ten included studies, nine mention an improvement in inhibitory control, six in selective attention, three in cognitive flexibility, and one in working memory (all p < 0.05). It was concluded that the practice of physical activity, exercise, or sport has a positive and significant effect on the executive functions of adults with ADHD, specifically on selective attention, inhibitory control, and cognitive flexibility. Furthermore, benefits were observed in depression, brain activation, and stability. Among the limitations is the lack of a meta-analysis, which makes it difficult to quantify and recommend which intervention is most effective for this population. Furthermore, the various types and degrees of ADHD were not considered. Full article

Background/Objectives: This article aims to investigate the multifaceted effects of alcohol on neurophysiopathological development from gestational stages through adult life and the consequent dynamic-relational challenges in individuals with Fetal Alcohol Spectrum Disorder (FASD). FASD, resulting from prenatal alcohol exposure (PAE), is characterized by a range of neurological, cognitive, behavioral, and sometimes physical impairments. This article explores how alcohol and its toxic metabolites cross the placenta, inducing direct cellular toxicity and epigenetic alterations that disrupt critical neurodevelopmental processes such as neurogenesis and brain circuit formation. Clinically, individuals with FASD exhibit diverse deficits in executive functioning, learning, memory, social skills, and sensory-motor abilities, leading to significant lifelong disabilities. A central focus is the application of the World Health Organization’s International Classification of Functioning, Disability and Health (ICF) criteria to comprehensively frame these disabilities. The ICF’s biopsychosocial model allows for a multidimensional assessment of impairments in body functions and structures, limitations in activities, and restrictions in participation, while also considering the crucial role of environmental factors. Methods: PubMed and Semantic Scholar databases were searched for relevant papers published in English. Results: This article highlights the utility of the ICF in creating individualized functioning profiles to guide interventions and support services, addressing the limitations of traditional assessment methods. Conclusions: While the ICF framework offers a robust approach for understanding and managing FASD, further research is essential to develop and validate FASD-specific ICF-based assessment tools to enhance support and social participation for affected individuals. Full article

Autism spectrum disorder (ASD) and Fragile X syndrome (FXS) are neurodevelopmental disorders marked by deficits in communication and social interaction, often accompanied by anxiety, seizures, and intellectual disability. FXS, the most common monogenic cause of ASD, results from silencing of the FMR1 gene and consequent loss of FMRP, a regulator of synaptic protein synthesis. Disruptions in cyclic nucleotide (cAMP and cGMP) signaling underlie both ASD and FXS contributing to impaired neurodevelopment, synaptic plasticity, learning, and memory. Notably, reduced cAMP levels have been observed in platelets, lymphoblastoid cell lines and neural cells from FXS patients as well as Fmr1 KO and dfmr1 Drosophila models, linking FMRP deficiency to impaired cAMP regulation. Phosphodiesterase (PDE) inhibitors, which prevent the breakdown of cAMP and cGMP, have emerged as promising therapeutic candidates due to their ability to modulate neuronal signaling. Several PDE isoforms—including PDE2A, PDE4D, and PDE10A—have been implicated in ASD, and FXS, as they regulate pathways involved in synaptic plasticity, cognition, and social behavior. Preclinical and clinical studies show that PDE inhibition modulates neuroplasticity, neurogenesis, and neuroinflammation, thereby ameliorating autism-related behaviors. BPN14770 (a PDE4 inhibitor) has shown promising efficacy in FXS patients while cilostazol, pentoxifylline, resveratrol, and luteolin have showed improvements in children with ASD. However, challenges such as isoform-specific targeting, optimal therapeutic window, and timing of intervention remain. Collectively, these findings highlight PDE inhibition as a novel therapeutic avenue with the potential to restore cognitive and socio-behavioral functions in ASD and FXS, for which effective targeted treatments remain unavailable. Full article

Background: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) survivors exhibit increased rates of psychological comorbidities, cognitive impairment (CI), and reduced health-related quality of life (HRQoL). This cross-sectional study investigated the prevalence of CI and its association with reduced HRQoL and depression among iTTP survivors. Methods: iTTP survivors completed the Beck Depression Inventory (BDI-II), the SF-36 for evaluation of HRQoL, and the NIH Toolbox Cognition Battery. SF-36 scores and fluid cognition and crystallized cognition composite scores from the cognition battery were compared to the reference population. We examined associations of cognitive impairment with depression and HRQoL. Results: We enrolled 47 patients with iTTP; 76.6% were female, the median age was 51 (IQR 39, 60), and the median number of episodes was 2 (1, 3.5). Compared to the reference, iTTP survivors had significantly lower mean scores in seven SF-36 domains (physical function, physical limitation, general, mental health, vitality, social functioning, and emotional limitation) as well as the mental component score (MCS) (p < 0.0001) and physical component scores (PCS) (p < 0.0001). A lower physical HRQoL score was observed in those with mild (49.3 vs. 37.7, p = 0.005) and major (49.3 vs. 38.4, p = 0.007) CI compared to no CI. The fluid cognition composite score correlated strongly with the SF-36 Physical Component Summary (r = 0.548, p = 0.0002) but not the Mental Component Summary (r = 0.113, p = 0.489). Conclusions: Cognitive impairment in iTTP survivors is associated with reduced physical HRQoL. Identifying and addressing cognitive deficits in iTTP may improve HRQoL. Given that 40% of participants had depressive symptoms, which were associated with reduced mental HRQoL, iTTP survivors may also benefit from routine mental health screening t. Full article

Background: Speech and Language Impairment (SLI) significantly affects children’s communication skills, limiting their social and academic development. Case Information: This single-case study evaluates the effects of a personalized intervention in a 9-year-old child diagnosed with SLI, integrating linguistic and cognitive strategies to remediate core deficits typically observed in children with SLI. Two main objectives were established: (1) to assess the child’s psycholinguistic competencies and cognitive processes and (2) to analyze the impact of the intervention on skills such as phonology, semantics, syntax, executive functions, and emotional well-being. The longitudinal and personalized design included pre- and post-intervention assessments conducted over two and a half years using tools such as the ITPA and Peabody Vocabulary Test. The intervention sessions were structured into linguistic and cognitive activities, with a frequency of two weekly language sessions and one cognitive functions session. Statistical analysis included ANOVA to evaluate significant changes. Conclusions: The results showed significant improvements in linguistic areas such as auditory comprehension (from 3–5 to 10 years) and verbal expression (from 5–10 to 9–6), as well as in cognitive aspects such as visuomotor sequential memory and visual comprehension, which exceeded the expected values for the child’s age. However, skills such as grammatical integration and auditory association did not show significant progress. This demonstrates that personalized and multidisciplinary interventions can considerably improve linguistic and cognitive abilities in children with SLI, although some areas require more specific approaches. The findings highlight implications for designing tailored intervention strategies, emphasizing the need for further research with larger samples and control groups to generalize the results. This case reaffirms the importance of comprehensive approaches in the treatment of SLI to maximize the academic and social development of affected children. Full article

Background/Objectives: Children and adolescents with neurodevelopmental disorders (NDDs) often experience deficits in executive functioning and emotional regulation, which impact their academic, social, and behavioral development. While physical activity is increasingly recognized as a promising non-pharmacological intervention, the specific effects on cognitive and emotional domains remain heterogeneous. This systematic review and meta-analysis aimed to assess the efficacy of physical–motor interventions in improving executive functions and emotional regulation in youths with NDDs. Methods: Following PRISMA 2020 guidelines, a comprehensive search of five databases was conducted (2010–2024) to identify randomized controlled trials (RCTs) evaluating the effects of structured physical activity programs on executive and emotional outcomes in children and adolescents diagnosed with NDDs. A total of 22 RCTs were included in the qualitative synthesis, while 16 were included in the quantitative analysis. Effect sizes were calculated using a random effects model, while heterogeneity was assessed with the Q, I², Tau², and Egger’s tests. Results: Physical activity interventions demonstrated a non-significant effect on executive functioning (g = 0.492; p = 0.215; 95% CI: −0.286 to 1.269). Although the point estimate suggested a small-to-moderate effect, the wide confidence interval and lack of statistical significance prevent firm conclusions. In contrast, a large and significant effect was observed on emotional regulation outcomes (g = −1.204; p < 0.001; 95% CI: −1.688 to −0.655), despite moderate heterogeneity (I² = 72.3%). Several studies also reported specific improvements in working memory, cognitive flexibility, and emotional control. Conclusions: Structured physical activity may be an effective complementary intervention for improving emotional regulation in youth with NDDs, with less consistent evidence for executive functioning. Future research should clarify optimal protocols and target populations to enhance intervention effectiveness. Full article

Background/Objectives: Loneliness is a common experience in adolescence, typically centered around difficulties in relationships with same-age peers and friends. It is often assumed that those diagnosed with autism and/or Attention-Deficit/Hyperactivity Disorder (ADHD) are at greater risk of loneliness than their non-diagnosed peers due to documented difficulties in making and maintaining friendships. Although quantitative research on loneliness and autism exists, there remains a notable gap in studies that explore the lived experiences of loneliness from the perspective of adolescents diagnosed with autism and ADHD, particularly in relation to their peers/or peers’ experiences. Method: To address this gap in the literature, 10 focus groups were conducted with adolescents diagnosed with autism and/or ADHD to discuss their experiences of loneliness. Results: Overall, young people with autism and ADHD did not consider loneliness to be a greater issue for them compared to their neurotypical peers. Six themes with five subthemes were developed through thematic analysis of the interview data: “not feeling like you belong when socializing”, “being alone can be a good thing but not when it’s not your choice”, “social media can be a good thing, but it’s not as good as in real life”, “not having anyone you can rely on to support you through tough times”, “school support can bring young people together”, and “sometimes it’s good to be distracted from negative thinking”. Conclusions: Although these themes are comparable to those emerging from research with non-autistic and non-ADHD youth, the importance of quality relationships with friends who provided support with daily functioning was viewed differently. Full article

Attention-deficit/hyperactivity disorder (ADHD) presents unique challenges for middle school students, a population navigating heightened academic, social, and emotional demands. This review examines empirical literature on school-based interventions targeting ADHD in middle school populations, a group often under-represented in intervention research. This review synthesizes findings from studies on academic accommodations, organizational training (e.g., HOPS), self-management strategies, mental health supports (e.g., CBT), and integrated programs like STAND and the Challenging Horizons Program. Evidence suggests that targeted school-based interventions can improve executive functioning, task engagement, academic performance, and social–emotional outcomes. However, interventions vary in efficacy depending on implementations’ fidelity, individual differences, and contextual supports (such as family involvement and school resources). Although promising, many interventions are limited by scalability, sustainability, and a lack of rigorous longitudinal data. This paper identifies critical gaps in middle school-specific research and highlights the need for future studies on long-term outcomes, student self-advocacy, and the reduction of stigma. Overall, this review underscores the potential of multi-component, school-based approaches to mitigate academic and behavioral challenges in middle school students with ADHD. We also call for expanded efforts to tailor and sustain these interventions in real-world educational settings. Full article