AbstractIt is well established that the left hemisphere is dominant for oral language production in the majority of neurotypical individuals, while a more symmetrical pattern of activation is observed in cases of conditions such as dyslexia. Cerebral lateralization of written language, however, despite the critical role of writing in education and in everyday communication and the fact that children with dyslexia present with writing difficulties, has been investigated by only a few studies, none of which has sampled children, neurotypical or not. Here we aim to investigate the cerebral lateralization of written language in 20 children at risk for dyslexia compared with 20 neurotypical children using functional transcranial Doppler ultrasonography. We hypothesized that the linguistic component of writing would be less lateralized in children at risk for dyslexia compared with controls; however, there was not enough evidence to either confirm or reject this hypothesis. Furthermore, we explored the correlation between writing competence and the cerebral lateralization of the linguistic component of written language, which, as hypothesized, were not correlated. These findings suggest that, in middle childhood, cerebral lateralization for the linguistic component of writing may not be a biomarker of dyslexia risk, highlighting the need for further research into alternative neural or cognitive mechanisms underlying reading difficulties. (Preregistered Stage 1 protocol: https://osf.io/u54tk (date of in-principle acceptance: 1 December 2022).)

Background/Objectives: Sensory processing constitutes a fundamental neurobiological mechanism that allows individuals to perceive, interpret, and respond adaptively to sensory input. Atypical patterns of sensory processing are frequently observed in neurodevelopmental disorders such as Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD). The purpose of this study was to evaluate the psychometric properties of the Greek Sensory Profile 2 Short Form following its linguistic and cross-cultural adaptation. Methods: An on-site parent-report survey was conducted among children and adolescents aged 3.0 to 14.11 years across Greece. The study included the Sensory Profile 2 Short Form (SSP2), the Child Behavior Checklist (CBCL), and the Social Communication Questionnaire (SCQ). A total of 350 parents participated in the study. Results: The present study demonstrated that the Greek version of the SSP2 possesses good psychometric properties. The results of the Exploratory Factor Analysis (EFA) of the 34 items explained 63.6% of the total variance. Internal consistency for both primary scales—Sensory (α = 0.93) and Behavioral (α = 0.96)—was satisfactory, as were the subscales Seeking (α = 0.88), Avoiding (α = 0.94), Sensitivity (α = 0.94), and Registration (α = 0.91). Significant correlations with the CBCL and SCQ supported convergent validity. The findings also highlighted associations with sociodemographic variables, providing insights into population-specific variations in sensory processing. Conclusions: The Greek version of the SSP2 demonstrates strong psychometric properties and is suitable for assessing sensory processing patterns in children and adolescents. Its use enables culturally appropriate screening for atypical sensory processing, informing both research and clinical practice and supporting early identification and intervention strategies.

Early life stress (ELS) and adverse childhood experiences are critical determinants of neurodevelopmental trajectories and long-term somatic and psychiatric health outcomes. This narrative review synthesizes current evidence, identified through searches in PubMed, Scopus, and Web of Science, on the neurobiological and epigenetic mechanisms through which early environmental exposures shape developmental programming and stress responsivity across the lifespan. A central framework is the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which mediates adaptive and maladaptive stress responses. During sensitive developmental periods, including prenatal, perinatal, and early postnatal stages, increased neuroplasticity confers heightened vulnerability to environmental influences, resulting in persistent alterations in stress regulation systems, brain circuitry, and endocrine function. The review further examines the role of maternal stress during gestation, with emphasis on placental regulatory mechanisms and fetal programming processes that establish long-term physiological set points. In parallel, emerging evidence on paternal stress is considered, highlighting potential contributions of germline epigenetic modifications and postnatal environmental transmission pathways. At the molecular level, epigenetic mechanisms-including DNA methylation, histone modifications, and non-coding RNA regulation-are discussed as key mediators linking early environmental exposures to stable changes in gene expression without alterations in DNA sequence. Collectively, the evidence supports ELS as a fundamental biological embedding process with enduring consequences for health across the lifespan. A deeper understanding of these mechanisms, alongside the identification of reliable biomarkers, is essential for early detection and the development of targeted preventive and intervention strategies in pediatric populations.

Type 1 diabetes (T1D) constitutes a chronic metabolic disorder attributed to the autoimmune destruction of insulin-producing pancreatic β cells, which most frequently occurs in childhood. Long-term complications of T1D are expected to occur mainly in adult life, whereas cognitive dysfunction can also occur in children and adolescents with T1D. Most studies demonstrate mild cognitive impairment, especially in the domains of memory, attention and executive functions, all of which affect academic performance, which may also negatively influence adherence to appropriate glucose monitoring and insulin treatment in children and adolescents with T1D. As a result, mild cognitive dysfunction can be an obstacle to both optimal glycemic control during childhood and adolescence and academic achievements for young individuals with T1D. The major metabolic changes occurring around the onset of diabetes, such as severe hyperglycemia and diabetic ketoacidosis, may have a negative impact on brain plasticity during this vulnerable period of neurodevelopment, especially in children diagnosed at a younger age. The pathophysiological mechanisms involved are closely related to increased oxidative stress and the accumulation of advanced glycation end products in the brain, thus leading to neuron cell damage and apoptosis. On the other hand, hypoglycemic episodes and glucose fluctuations may also impair neuronal integrity. The aim of the current narrative review is therefore to present the existing literature data on the clinical aspects, risk factors and molecular mechanisms associated with cognitive dysfunction in children and adolescents with T1D.

Prenatal psychological distress may affect maternal well-being and fetal outcomes. The Pregnancy Experience Scale–Brief Version (PES-Brief) captures both positive (uplifts) and negative (hassles) experiences during pregnancy, providing insight into maternal emotional appraisal. Longitudinal observational validation study. To translate, culturally adapt, and validate the PES-Brief in the Greek language. A total of 156 primiparous pregnant women completed the PES-Brief at two time points: 15th–20th weeks of gestation (Phase A) and 36th–38th weeks (Phase B). Psychometric analyses were conducted using Phase A data, while Phase B data were used to explore longitudinal responsiveness. PES-Brief scores were correlated with perceived stress assessed with the Perceived Stress Scale-14 (PSS-14), and anxiety assessed with the State-Trait Anxiety Inventory (STAI-I and STAI-II). Psychometric evaluation included internal consistency, construct validity (exploratory factor analysis), and convergent validity with perceived stress and anxiety. Exploratory factor analysis supported the original two-factor structure of uplifts and hassles. PES-Brief subscale scores were significantly associated with perceived stress and anxiety, supporting convergent validity. Statistically significant changes were observed between early-to-mid and late pregnancy (Phase A and Phase B). The Greek PES-Brief demonstrated satisfactory internal consistency, a clear two-factor structure, and meaningful longitudinal correlations across gestational stages. It represents a reliable tool for assessing pregnancy-related emotional experiences in research and clinical settings.

Background: An increasing amount of evidence, derived from both human epidemiological studies and animal research, suggests that exposure to maternal obesity in utero is linked to adverse neurodevelopmental outcomes in the offspring. These can include attention deficit hyperactivity disorder, autism spectrum disorders, intellectual disability, and cerebral palsy. Methods: A thorough search in Medline/PubMed and Google Scholar databases was performed by two independent reviewers in order to investigate the link between the exposure to maternal obesity and neurodevelopmental outcomes in the offspring. A list of keywords, including maternal obesity, maternal overweight, maternal diet, neurodevelopment, and neuropsychiatric disorders, was used in the search algorithm. Results: The existing evidence regarding the potential mechanisms through which maternal obesity may impact offspring neurodevelopment and programming, such as inflammation, hormone dysregulation, alterations to the microbiome, and epigenetics, as well as evidence from animal studies, was summarized in this narrative review. Conclusions: Maternal obesity seems to be overall associated with various neuropsychiatric and neurodevelopmental disorders. However, more robust data from future studies are needed to establish this association, which will take into account the role of potential confounders such as genetic factors and gene–environment interactions.

Background: With its abrupt and huge health and socio-economic consequences, the coronavirus disease (COVID-19) pandemic has led to a uniquely demanding, intensely stressful, and even traumatic period. Healthcare workers (HCW), especially nurses, were exposed to mental health challenges during those challenging times. Objectives: Review the current literature on mental health problems among nurses caring for COVID-19 patients. Methods: This is a narrative review and critical evaluation of relevant publications. Results: Nurses experienced higher levels of stress, burnout, anxiety, depression, frustration, stigma, and depersonalization compared to other HCW. Factors that increased this symptomatology included concerns about infection or infection of family members, inadequate staff protective equipment, extended working hours, insufficient information, a reduced sense of security, and post -traumatic stress disorder. The factors that improved the psychopathology included a general positive attitude, job satisfaction, adequate information and education, harmonious group relationships, post -traumatic development, emotional intelligence, psychological counseling, mindfulness -based stress reduction, stable leadership, guidance, and moral and practical administrative support. Conclusions: Recent studies clearly show that nurses, especially women, are the most vulnerable subgroup among HCW and are particularly prone to mental health impacts during the COVID-19 pandemic. The documented mental health vulnerability of frontline nursing staff during the COVID-19 pandemic requires preventive nursing management actions to increase resilience and to develop relevant defense mechanisms.

Background: Functional Gastrointestinal Disorders (FGIDs) present a higher prevalence in individuals with Neurodevelopmental Disorders (NDDs). The Stress System and the Gut–Brain axis (GBA) may mediate these relations. We aimed to assess the prevalence and profile of FGIDs in a clinical sample of children with Autism Spectrum Disorder (ASD) and Attention Deficit/Hyperactivity Disorder (ADHD) compared to typically developing children (TD) as well as to investigate possible relations between stress-related biomarkers and internalizing/externalizing problems in children with NDDS. Methods: In total, 120 children, aged between 4 and 12 years old, formed three groups (N = 40, each): ADHD, ASD and TD. Salivary cortisol, hair cortisol and serum leptin were measured. Results: The ASD group had more FGID problems than the TD group (p = 0.001). The ADHD and ASD groups had higher total internalizing/externalizing problems than the TD group (p < 0.0001, p < 0.0001, p = 0.005, respectively). Children with FGIDs showed more total, internalizing and externalizing problems compared to children without FGIDs (p < 0.0001, p < 0.0001, p = 0.041, respectively). The ADHD group showed lower AUCg values (p < 0.0001), while the hair cortisol was higher for the TD group (p < 0.0001). Conclusion: In conclusion, children with NDDs had more FGID symptoms and present higher internalizing and externalizing problems. Children with ADHD and FGIDs had more internalizing problems compared to those without FGIDs. No differences in stress-related biomarkers were shown to differentiate children with NDDs with and without FGIDs. Future prospective studies including a greater number of children may elucidate the biological pathways linking these comorbidities.

Our internal balance, or homeostasis, is threatened or perceived as threatened by stressful stimuli, the stressors. The stress system is a highly conserved system that adjusts homeostasis to the resting state. Through the concurrent activation of the hypothalamic-pituitary-adrenal axis and the locus coeruleus/norepinephrine-autonomic nervous systems, the stress system provides the appropriate physical and behavioral responses, collectively termed as "stress response", to restore homeostasis. If the stress response is prolonged, excessive or even inadequate, several acute or chronic stress-related pathologic conditions may develop in childhood, adolescence and adult life. On the other hand, earlylife exposure to stressors has been recognized as a major contributing factor underlying the pathogenesis of non-communicable disorders, including neurodevelopmental disorders. Accumulating evidence suggests that early-life stress has been associated with an increased risk for attention deficit hyperactivity disorder and autism spectrum disorder in the offspring, although findings are still controversial. Nevertheless, at the molecular level, early-life stressors alter the chemical structure of cytosines located in the regulatory regions of genes, mostly through the addition of methyl groups. These epigenetic modifications result in the suppression of gene expression without changing the DNA sequence. In addition to DNA methylation, several lines of evidence support the role of non-coding RNAs in the evolving field of epigenetics. In this review article, we present the anatomical and functional components of the stress system, discuss the proper, in terms of quality and quantity, stress response, and provide an update on the impact of early-life stress on child development and behavior.

Childhood obesity is a complex disease with multiple biological and psychosocial risk factors. Recently, novel digital programs were developed with growing evidence for their effectiveness in pediatric weight management studies. The ENDORSE platform consists of mobile applications, wearables, and serious games for the remote management of childhood obesity. The pilot studies included 50 mothers and their children aged 6–14 years and resulted in a clinically significant BMI z-score reduction over 4 to 5 months. This secondary analysis of the ENDORSE study focuses on parenting styles and psychosocial factors. Methodology: Semi-structured clinical interviews were conducted with all participating mothers pre-and post-intervention. The Parenting Styles and Dimensions Questionnaire (PSDQ) evaluated the mothers’ parenting styles. The psychosocial functioning of the participating children was assessed with the parental version of the Strengths and Difficulties Questionnaire (SDQ). The relationship between parenting styles, psychosocial parameters, and weight outcomes was investigated using a linear regression analysis. Results: Weight-related stigma at school (56%), body image concerns (66%), and difficulties in family relationships (48%) were the main concerns documented during the initial psychological interviews. According to the SDQ, there was a significant decrease in children’s conduct problems during the study’s initial phase (pre-pilot group). A decrease in maternal demandingness (i.e., strict parenting style) was associated with a decrease in BMI z-score (beta coefficient = 0.314, p-value = 0.003). Conclusion: Decreasing parental demandingness was associated with better weight outcomes, highlighting the importance of assessing parenting factors in pediatric weight management programs.

Dysregulation of the stress system via incidental long exposure to glucocorticoids (GCs) can lead to weight gain. In addition, family and maternal stress can also have an impact on children’s weight. Hair is used in several studies to evaluate cortisol (GC) levels in children and adolescents with excess weight as a retrospective stress biomarker, depending on the hair length the cortisol measurement depicting different time periods. We aimed to investigate whether there is a difference among segmental hair cortisol concentration (HCC) analysis between children and adolescents with overweight and obesity, their mothers, and normal weight peers. This study recruited 25 children aged 6–14 years with a body mass index (BMI) ≥ 85th centile and their mothers, as well as 20 children of the same age with a BMI < 85th centile. Hair cortisol concentration was measured using electrochemiluminescence immunoassay. Segmental HCC analysis exhibited gradually decreasing values in all participants as segments of hair were more distantly located from the scalp. A positive correlation was found between BMI z-score and HCC of the first segment of hair in children and adolescents with elevated BMI (b = 1.84, p = 0.033), as well as with maternal HCC / of an only child (b = 15.77, p = 0.01). There were no associations between mother-child dyads and children and adolescents of different BMI groups, even though minors with excess weight exhibited higher HCC levels in all segments of hair in comparison to their normal weight counterparts. Hair cortisol of all participants exhibited a gradually declining concentration. More studies with larger samples and more sensitive methods of analysis are warranted in order to draw firmer conclusions.

Background Heterogeneous mental health outcomes during the COVID-19 pandemic are documented in the general population. Such heterogeneity has not been systematically assessed in youth with autism spectrum disorder (ASD) and related neurodevelopmental disorders (NDD). To identify distinct patterns of the pandemic impact and their predictors in ASD/NDD youth, we focused on pandemic-related changes in symptoms and access to services. Methods Using a naturalistic observational design, we assessed parent responses on the Coronavirus Health and Impact Survey Initiative (CRISIS) Adapted For Autism and Related neurodevelopmental conditions (AFAR). Cross-sectional AFAR data were aggregated across 14 European and North American sites yielding a clinically well-characterized sample of N = 1275 individuals with ASD/NDD (age = 11.0 ± 3.6 years; n females = 277). To identify subgroups with differential outcomes, we applied hierarchical clustering across eleven variables measuring changes in symptoms and access to services. Then, random forest classification assessed the importance of socio-demographics, pre-pandemic service rates, clinical severity of ASD-associated symptoms, and COVID-19 pandemic experiences/environments in predicting the outcome subgroups. Results Clustering revealed four subgroups. One subgroup— broad symptom worsening only (20%)—included youth with worsening across a range of symptoms but with service disruptions similar to the average of the aggregate sample. The other three subgroups were, relatively, clinically stable but differed in service access: primarily modified services (23%), primarily lost services (6%), and average services/symptom changes (53%). Distinct combinations of a set of pre-pandemic services, pandemic environment (e.g., COVID-19 new cases, restrictions), experiences (e.g., COVID-19 Worries), and age predicted each outcome subgroup. Limitations Notable limitations of the study are its cross-sectional nature and focus on the first six months of the pandemic. Conclusions Concomitantly assessing variation in changes of symptoms and service access during the first phase of the pandemic revealed differential outcome profiles in ASD/NDD youth. Subgroups were characterized by distinct prediction patterns across a set of pre- and pandemic-related experiences/contexts. Results may inform recovery efforts and preparedness in future crises; they also underscore the critical value of international data-sharing and collaborations to address the needs of those most vulnerable in times of crisis.

Childhood obesity is a serious public health problem worldwide. The ENDORSE platform is an innovative software ecosystem based on Artificial Intelligence which consists of mobile applications for parents and health professionals, activity trackers, and mobile games for children. This study explores the impact of the ENDORSE platform on metabolic parameters associated with pediatric obesity and on the food parenting practices of the participating mothers. Therefore, the metabolic parameters of the 45 children (mean age: 10.42 years, 53% girls, 58% pubertal, mean baseline BMI z-score 2.83) who completed the ENDORSE study were evaluated. The Comprehensive Feeding Practices Questionnaire was used for the assessment of food parenting practices. Furthermore, regression analysis was used to investigate possible associations between BMI z-score changes and changes in metabolic parameters and food parenting practices. Overall, there was a statistically significant reduction in glycated hemoglobin (mean change = −0.10, p = 0.013), SGOT (mean change = −1.84, p = 0.011), and SGPT (mean change = −2.95, p = 0.022). Emotional feeding/food as reward decreased (mean change −0.21, p = 0.007) and healthy eating guidance increased (mean change = 0.11, p = 0.051). Linear regression analysis revealed that BMI z-score change had a robust and significant correlation with important metabolic parameters: HOMA-IR change (beta coefficient = 3.60, p-value = 0.046), SGPT change (beta coefficient = 11.90, p-value = 0.037), and cortisol change (beta coefficient = 9.96, p-value = 0.008). Furthermore, healthy eating guidance change had a robust negative relationship with BMI z-score change (beta coefficient = −0.29, p-value = 0.007). Conclusions: The Endorse digital weight management program improved several metabolic parameters and food parenting practices.

Preeclampsia is a multisystemic clinical syndrome characterized by the appearance of new-onset hypertension and proteinuria or hypertension and end organ dysfunction even without proteinuria after 20 weeks of pregnancy or postpartum. Residing at the severe end of the spectrum of the hypertensive disorders of pregnancy, preeclampsia occurs in 3 to 8% of pregnancies worldwide and is a major cause of maternal and perinatal morbidity and mortality, accounting for 8–10% of all preterm births. The mechanism whereby preeclampsia increases the risk of the neurodevelopmental, cardiovascular, and metabolic morbidity of the mother’s offspring is not well known, but it is possible that the preeclamptic environment induces epigenetic changes that adversely affect developmental plasticity. These developmental changes are crucial for optimal fetal growth and survival but may lead to an increased risk of chronic morbidity in childhood and even later in life. The aim of this review is to summarize both the short- and long-term effects of preeclampsia on offspring based on the current literature.

BACKGROUND:Early life stress (ELS) describes a broad spectrum of adverse and stressful prenatal events, namely, prenatal maternal stress (PMS), or early postnatal events, which can have detrimental long-term influences on the physiology, cognition, and behavior of an individual. There is abundant evidence indicating that ELS exerts its lasting effects on the physical and mental health of the individual, likely acting through a number of mediating mechanisms, including the disruption of developmental programming of the fetus. Neurodevelopmental disorders (NDDs), for example, attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), are a group of conditions that typically manifest during infancy, childhood, or adolescence and are characterized by developmental deficits in various domains.SUMMARY:The scope of the current mini-review is to provide an up-to-date summary of the findings regarding the association of ELS and NDDs and the possible hormonal mechanisms through which PMS exerts its impact on neurodevelopment. We focus on the available evidence regarding children and adolescents diagnosed with ADHD or ASD. ELS exposure during developmental vulnerability windows may increase the risk for either subclinical neuropsychological alterations or clinical conditions, such as NDDs. In fact, a large body of evidence underlies the association of ELS exposure and increased risk for NDDs in the offspring.KEY MESSAGES:The majority of data suggest that ELS, including PMS, may be associated with ADHD and ASD in the offspring, although there is no consensus regarding the critical developmental periods. Carefully controlled prospective studies are needed to determine the possible causal processes and mechanisms underlying the association of ELS and NDDs.

Childhood obesity constitutes a major risk factor for future adverse health conditions. Multicomponent parent–child interventions are considered effective in controlling weight. Τhe ENDORSE platform utilizes m-health technologies, Artificial Intelligence (AI), and serious games (SG) toward the creation of an innovative software ecosystem connecting healthcare professionals, children, and their parents in order to deliver coordinated services to combat childhood obesity. It consists of activity trackers, a mobile SG for children, and mobile apps for parents and healthcare professionals. The heterogeneous dataset gathered through the interaction of the end-users with the platform composes the unique user profile. Part of it feeds an AI-based model that enables personalized messages. A feasibility pilot trial was conducted involving 50 overweight and obese children (mean age 10.5 years, 52% girls, 58% pubertal, median baseline BMI z-score 2.85) in a 3-month intervention. Adherence was measured by means of frequency of usage based on the data records. Overall, a clinically and statistically significant BMI z-score reduction was achieved (mean BMI z-score reduction −0.21 ± 0.26, p-value < 0.001). A statistically significant correlation was revealed between the level of activity tracker usage and the improvement of BMI z-score (−0.355, p = 0.017), highlighting the potential of the ENDORSE platform.

This paper presents a novel Procedural Content Generation (PCG) method aiming at achieving personalization and adaptation in serious games (SG) for health. The PCG method is based on a genetic algorithm (GA) and provides individualized content in the form of tailored messages and SG missions, taking into consideration data collected from health-related sensors and user interaction with the SG. The PCG method has been integrated into the ENDORSE platform, which harnesses the power of artificial intelligence (AI), m-health and gamification mechanisms, towards implementing a multicomponent (diet, physical activity, educational, behavioral) intervention for the management of childhood obesity. Within the use of the ENDORSE platform, a pre-pilot study has been conducted, involving the recruitment of 20 obese children that interacted with the platform for a period of twelve weeks. The obtained results, provide a preliminary justification of PCG’s effectiveness in terms of generating individualized content with sufficient relevance and usefulness. Additionally, a statistically significant correlation has been revealed between the content provided by the proposed PCG technique and lifestyle-related sensing data, highlighting the potential of the PCG’s capabilities in identifying and addressing the needs of a specific user.