Surgery is an anxiety-provoking event, but there are individual differences in the magnitude of experienced anxiety. The objective of this study was to identify patterns of children's preoperative anxiety, its predictors, and perioperative outcomes. The sample included 171 children (Mage = 9.95 years) undergoing elective surgery. We derived groups of children's anxiety based on multiple indicators (i.e., self-report, heart rate, and frontal brain EEG activity) during a preoperative visit and on the day of surgery. Parents and children reported on children's temperament, children's behavior was coded in the operating room, and postoperative pain ratings were collected. Two latent profiles of children were identified, including a subset with relatively average anxious responses across indicators (74%) and a subset with relatively heightened anxious responses across indicators (26%). Children in the heightened anxiety subgroup had higher levels of temperamental shyness, displayed greater observed distress behaviors (e.g., resistance to anesthesia, screaming) upon operating room entry, and tended to have higher levels of postoperative pain compared to children in the average anxiety subgroup. These results reveal child-level predictors and perioperative outcomes associated with the experience of elevated anxiety in the surgical context.
Evolutionary-developmental theories of stress responsivity contend that the in utero environment shapes offspring biobehavioral regulation in a manner that promotes postnatal functioning. To elucidate how the prenatal environment influences stress regulation, this study tested associations of maternal psychological distress and inflammation during pregnancy, based on both levels and changes over time, with infant behavioral stress regulation (n = 118). In early, mid, and late pregnancy, mothers reported on depressive and anxiety symptoms and completed blood draws that were assayed for pro-inflammatory cytokines (IL-6, TNF-⍺). When infants were 1 month old, research staff administered a heel stick blood draw and coded infant behavioral responses. Greater increases in maternal depressive symptoms and IL-6 from early to late pregnancy were associated with greater behavioral reactivity to and recovery from the heel stick. Conversely, higher overall levels of IL-6 predicted lower infant behavioral arousal. Maternal anxiety symptoms during pregnancy did not directly predict infant behavioral regulation, but there was evidence that overall levels of prenatal anxiety predicted infant behavior indirectly via IL-6. Anxiety symptom levels were associated with TNF-⍺. Findings add to evidence on prenatal origins of offspring behavioral regulation and suggest that changes in psychobiological processes over the course of pregnancy may distinctly predict infant outcomes.
Human perceptual abilities evolve throughout development, particularly with regard to processing complex stimuli. While many studies have investigated age-related changes in olfactory sensitivity, none have examined how developmental stages influence the perception of odor mixtures at the elemental and configural levels. In this study, we evaluated how children, teenagers, and adults (mean ages: 10, 15, and 39 years) perceive odor mixtures known to trigger either elemental or configural processing in adults. Two binary mixtures (AB and AB') and two senary mixtures (RC and RC'), known to elicit distinct perceptual strategies in adults, were evaluated using three tasks: typicality rating, target detection, and complexity evaluation. Results showed that perception of the senary mixtures remained consistent across age groups, indicating stable processing of these complex mixtures. In contrast, age-related differences emerged for the binary mixtures. Children perceived AB as less complex than AB', but did not rate it as more typical of the configural odor, whereas adults rated AB as more typical of this odor than AB' and tended to show reduced access to mixture components in binary mixtures, with teenagers displaying an intermediate profile. Overall, these findings suggest developmental changes in odor mixture processing, consistent with a progressive shift from more elemental to more configural olfactory strategies, particularly for mixtures of lower chemical complexity.
Although exposure to violence has been linked to executive functioning impairments, the biological mechanisms underlying this association remain unclear. This study examined CpG sites associated with executive functions in 78 young adults and their links to family (psychological and physical) and community violence during childhood. The scales used were Conflict Tactics (family violence); Things I Have Seen and Heard (community violence); Barkley Deficits in Executive Functioning. Mean differences (Mann-Whitney-U/Kruskal-Wallis) and Spearman correlations were assessed. An epigenome-wide association study identified differentially methylated CpGs, and linear regressions examined associations with violence exposures. Girls reported more family and psychological violence. Black participants experienced higher family violence. Executive dysfunction (ED) correlated with psychological family and community violence, and family violence forms were interrelated. Differentially methylated positions highlighted genes tied to key biological processes: MRGPRD (sensory neurons development); DPPA3 (germ-cell development); UNKL (cell differentiation); GPR6 (learning and memory); DUSP5 (cell proliferation and differentiation); and CAPN13 (signal transduction, cytoskeletal remodeling and cell differentiation). Candidate gene analysis found associations between executive dysfunction and methylation levels in these genes. Exploratory pathway analysis suggested enrichment of neurodevelopment and synaptic plasticity, intracellular trafficking and cytoskeletal remodeling, genome stability and cellular stress responses, and neuroimmune and inflammatory signaling. These findings suggest associations between ED, childhood violence exposure, and differential DNA methylation in cognition- and health-related genes, suggesting that epigenetic markers may be associated with pathways linking early adversity to later outcomes, although no causal inference can be drawn.
Maternal prenatal docosahexaenoic acid (DHA) intake is critical for fetal brain and retinal development; however, evidence regarding its effects on offspring neurodevelopment and growth remains inconsistent. This systematic review and meta-analysis evaluated the efficacy of prenatal DHA supplementation on offspring neurodevelopmental outcomes (attention, motor, intelligence, language, executive function, and short-term memory) and growth parameters (birth weight, head circumference, gestational age, and birth length) in the general population. We analyzed randomized controlled trials (RCTs) from 2001 to 2023 across PubMed, Embase, and the Cochrane Library. Of 917 records, 21 RCTs were included in the systematic review, of which 19 were eligible for meta-analysis. The meta-analysis showed that prenatal DHA supplementation had no significant benefits on any neurodevelopmental outcome. Subgroup analyses revealed no improvements across all assessed domains (all p > 0.05). In contrast, prenatal DHA supplementation significantly increased neonatal birth weight (mean difference [MD] = 72.51 g, 95% CI: 37.55-107.48), whereas no notable improvements were observed in head circumference, gestational age, birth length, or any of the assessed neurodevelopmental outcomes. Overall, the current evidence does not support benefits of prenatal DHA supplementation for neurodevelopmental outcomes or for growth outcomes other than birth weight in the general population. Future research should focus on identifying subgroups that may be responsive to DHA based on genetic, nutritional, or environmental factors.
Resource scarcity paradigms are widely used to model environmentally induced disruptions in rodent maternal behavior. Yet, the critical methodological variable of bedding substrate type has received limited attention despite substantial variation in its use across laboratories. This study examined how two distinct bedding types (corncob, cellulose) interact with scarcity-adversity to influence maternal behavior in postpartum rats. We report that scarcity-adversity reliably increased insensitive pup-directed behaviors, elevated stress-related behaviors (tail biting/chasing), and impaired pup retrieval performance across both bedding types, confirming that resource scarcity disrupts maternal care regardless of substrate. However, the specific pattern of behavioral effects differed across bedding conditions. Increases in pup shoving were specific to scarcity-adversity dams in corncob bedding, whereas increases in anogenital licking of pups were specific to scarcity-adversity dams in cellulose bedding. Independent of adversity, cellulose dams displayed greater percentages of time spent grooming pups and nest building, while corncob dams displayed greater percentages of time spent nursing. In the pup retrieval test, cellulose dams exhibited longer latencies to retrieve 70% of pups than corncob dams. Together, these findings suggest that while core scarcity-adversity effects on insensitive pup-directed behaviors and pup retrieval generalize across these two substrates, bedding properties shape the specific expression of maternal behavioral disruption. Cellulose bedding may partially buffer certain aspects of intended adversity through compensatory caregiving, while corncob bedding may compound adversity through substrate discomfort. We recommend reporting bedding type in resource scarcity studies to facilitate cross-laboratory comparisons and ensure substrate characteristics align with experimental goals when modeling postpartum environmental adversity.
Infant socioemotional development has important implications for later functioning, reflecting capacities for emotional regulation, stress responsivity, and social engagement. Stress and mental health during pregnancy and the postpartum can adversely influence infant socioemotional functioning. This study examined whether postpartum depressive and anxiety symptoms mediate associations between prenatal maternal hair cortisol concentration (HCC) and infant socioemotional development. A sample of 128 participants was followed from the third trimester of pregnancy to 6 months postpartum. Maternal HCC was collected during the third trimester to reflect cortisol during the second half of pregnancy. Symptoms of depression and anxiety were measured at 2 weeks postpartum, and infant socioemotional problems were assessed at 6 months of age. Structural equation modeling tested postpartum depression and anxiety as parallel mediators. Results indicated that lower HCC in pregnancy predicted greater postpartum depression (B = -3.676, p = 0.003) and anxiety (B = -3.41, p = 0.009); depression was associated with greater infant socioemotional problems at 6 months (B = 1.900, p < 0.001). HCC was not directly associated with infant socioemotional outcomes (B = 1.071, p = 0.792); however, the indirect effect, through depressive symptoms, was significant (B = -6.99, p = 0.01). These findings suggest that prenatal physiological stress may influence infant socioemotional development indirectly through early postpartum depressive symptoms, highlighting the importance of integrated perinatal processes.
Pregnancy represents a critical juncture for intergenerational transmission of stress-related health vulnerabilities when child-bearers' history of maltreatment may precipitate stress responses that adversely impact maternal and fetal outcomes. We aimed to shed light on this path by testing hypotheses that (1) childhood maltreatment would predict oral inflammatory responses to acute stress in late pregnancy, and (2) these inflammatory responses would relate to subsequent obstetric complications. Hypotheses were tested in a community sample of women (n = 158) from a larger longitudinal study. Participants reported a history of maltreatment and completed the Trier Social Stress Test during the third trimester of pregnancy. Five saliva samples collected before and after the task were assayed for pro-inflammatory cytokines (IL1β, IL6, TNFα) and C-reactive protein (CRP) to index oral inflammation. At 3 months postnatal, women reported pregnancy and birth complications, and birth outcomes. Multilevel models of inflammatory response trajectories supported hypothesized paths: Greater childhood maltreatment-especially physical neglect and sexual abuse-predicted higher and/or extended inflammatory stress responses. In turn, higher inflammatory stress responses related to greater pregnancy and birth complications, and extended inflammatory responses related to a greater likelihood of preterm birth. Findings support oral inflammatory response to stress as a potential link to target in intergenerational health risk transmission.
Autism Spectrum Disorders (ASD) are a heterogeneous group of neurodevelopmental conditions characterized by deficits in social communication and the presence of restricted, repetitive behaviors. While genetic factors contribute substantially to ASD etiology, growing evidence highlights the role of environmental and epigenetic factors, with maternal stress during pregnancy emerging as a potential determinant of fetal brain development. Prenatal stress may alter the intrauterine environment through modulation of the hypothalamic-pituitary-adrenal (HPA) axis and changes in glucocorticoid signaling. These physiological responses have been associated with epigenetic modifications, such as DNA methylation, histone post-translational modifications, and alterations in non-coding RNA expression although causal pathways remain under investigation. Consequently, gene expression programs critical for neuronal proliferation, migration, synaptogenesis, and stress-response maturation are reshaped. Converging evidence from human cohorts and animal models indicates that these stress-induced epigenetic changes affect genes such as NR3C1, FKBP5, BDNF, OXTR, and SHANK3, contributing to altered stress response, impaired synaptic plasticity, and disrupted neural connectivity. Foundational studies before 2020 established the basic mechanistic link between prenatal stress, glucocorticoid exposure, and epigenetic gene regulation, forming a basis for the 2020-2025 literature summarized here. This narrative review synthesizes research published between 2020 and 2025, integrating molecular, epidemiological, and neurodevelopmental perspectives to elucidate how prenatal stress induces lasting neurobiological changes, thereby advancing the conceptual framework for early detection and intervention in ASD.
Stress can negatively impact caregiving behavior; while chronic stress is consistently associated with reduced caregiver sensitivity, evidence regarding acute stress remains mixed. This preregistered study examined the causal effects of acute psychosocial stress on caregiver sensitivity with an experimental pseudorandomized design. Female participants (N = 130, M age = 21.16, SD = 1.65) were assigned to either an adapted Trier Social Stress Test or a control condition, and then interacted with an infant simulator while their caregiver sensitivity was observed. We also investigated the role of situational empathic behavior and trait empathic concern in the relationship between acute stress and caregiver sensitivity. Structural equation modeling demonstrated that acute stress did not significantly decrease caregiver sensitivity. Furthermore, situational empathic behavior did not explain how acute stress affected caregiver sensitivity, nor did trait empathic concern influence how acute stress affected situational empathic behavior. However, trait empathic concern was positively associated with caregiver sensitivity, affirming that empathy is fundamental to caregiving. We discuss that effects of acute stress may be more subtle compared to chronic stress and highlight the importance of sensitive measurement instruments in continued research, which will help us to further understand how stress impacts caregiving and, consequently, child outcomes.
Idiopathic toe walking (ITW) is a diagnosis given to children who walk with an absence of heel strike in the contact phase of the gait cycle, who are otherwise typically developing. This study aimed to determine if children with ITW had cortical activation differences when completing a tactile sensation test compared to typically developing children. The study included 15 typically developing children and 15 children with ITW. Participants were required to perform a two-point discrimination test during an fMRI using a standard block design.Four clusters were identified, where the controls exhibited significantly greater activation than the ITW group during the tactile test. The largest cluster peaked in the right inferior frontal gyrus. A second cluster was centered in the right middle frontal gyrus. The third cluster peaked in the right inferior parietal lobule. Lastly, a smaller cluster was identified in the right precuneus.The results indicate that the control group exhibited greater activation than the ITW group in key brain regions involved in executive function, motor planning, and sensory integration. These findings support the notion that ITW is linked to functional differences in neural networks related to motor control and sensory integration.
The oxytocin system is central to regulating social behaviors, with genetic variations in the oxytocin receptor gene (OXTR), particularly the rs53576 single nucleotide polymorphism (SNP), linked to individual differences in emotional reactivity and social cognition. GG genotype carriers typically show heightened sensitivity to social dynamics, exhibiting greater empathy and prosocial behaviors in positive contexts but also increased anxiety and emotional dysregulation in response to negative social stressors, such as ostracism. Although these associations are well established in adults, little is known about the impact of genetic variability in the oxytocin system on infants' behavioral and emotional reactivity to ostracism experiences. The current study investigated whether rs53576 allelic variations influence 13-month-olds' (N = 56, 41% males; mostly White) affective and behavioral reactions to ostracism episodes during a live-triadic ball-tossing game. Results demonstrated that GG carriers show heightened sensitivity to ostracism compared to AA/AG carriers. Specifically, ostracized GG infants exhibited a more pronounced decrease in Positive Emotionality and an increase in Negative Emotionality. Current findings underscore the role of genetic predispositions in enhancing sensitivity to social experiences, shaping infants' early interactions within their social environment.
There are age and sex differences in the processing of social reward, although the basis for these differences is not well established. We previously found greater social motivation at P50 (postpubertal adolescence) than at P70 (adulthood), and that female rats showed greater social motivation than male rats. Thus, we investigated whether gonadal hormones may contribute to age and sex differences in social reward motivation. Rats underwent either gonadectomy or sham surgery at P41 (adolescent group) or P69 (adult group) and began testing in the operant conditioning paradigm 5 days later. When trained on a fixed ratio of one, gonadectomized rats had a greater social preference relative to control rats, irrespective of sex and age. When tested on a progressive ratio (effort required to access social reward continually increased), adolescents were more motivated than were adults, irrespective of sex or gonadal status. However, resistance to extinction was evident in gonadectomized rats relative to control rats, irrespective of sex and age. Thus, the results provide evidence that gonadal hormones influence social preference, although not social motivation. Ongoing maturation, rather than puberty, is responsible for age-related changes in social reward motivation, and the presence of gonadal hormones independently influences the preference for a social partner.
Proficiency in fine motor skills improves significantly from childhood into adolescence; however, a longitudinal approach has not been used to examine the maturation trajectory of eye-hand coordination. Capturing individual performance changes by following the same cohort over time could offer unique insight into the developmental processes. This study assessed eye and hand kinematics during the execution of a prehension task in typically developing children (n = 17) tested at two time points: middle childhood (mean age: 9.14 years) and adolescence (mean age: 13.51 years). Results showed significant improvement in overall performance, which was due to shorter fixation duration, faster reaching duration, and shorter object placement duration. Temporal pattern of eye-hand coordination became more mature (adult-like) when picking up an object, indicating efficient coordination between the grasp and reach movements. Results demonstrate that kinematic analysis of prehension and eye-hand coordination provides a sensitive assay of the maturation trajectory of visuohaptic integration during prehension. These findings may support new methods for assessing fine motor skills and enhance the diagnosis of neurodevelopmental disorders linked to visuomotor impairments.
Early life stress, caused by maternal separation (MS), increases hippocampal inflammatory markers in neonates. However, the effects of MS on hypothalamic neuroimmune development and the peripheral immune response have not yet been assessed. This study examined the effect of MS on neuroimmune and synaptic development by evaluating the expression of pro- and anti-inflammatory cytokines and their association with synaptic plasticity markers in the hypothalamus and hippocampus throughout postnatal development. Microglial activation was analyzed in both brain regions at postnatal day 15 (P15), and the systemic immune response was measured through hemolytic capacity. Cytokine and synaptophysin expression showed dynamic, region-specific changes across postnatal development. MS reduced hypothalamic interleukin 6 expression at P6 and P12, enhanced microglial activation at P15, and blunted the developmental increase in hemolytic capacity seen in controls at P21. While control animals exhibited region-specific associations between cytokines and synaptic markers, these relationships were attenuated in the MS group, including a differential interleukin 6-synaptophysin association. These results suggest that MS alters hypothalamic neuroimmune relationships and systemic immune responses during critical developmental windows. Additionally, increased microglial activation at P15 suggests that MS induced proinflammatory, region-specific changes. These alterations may contribute to heightened vulnerability to mental disease later in life.
A growing number of studies examined the neural correlates of insecure attachment dimensions. Attachment strategies can shift across the lifespan as individuals encounter new interpersonal and emotional experiences. Additionally, neural changes during development may influence these strategies. A systematic review and an activation likelihood estimation meta-analysis were conducted to examine the associations between insecure attachment dimensions and brain activations during socio-affective stimuli tasks according to age. The review adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered on PROSPERO. The research identified 1743 articles, of which 15 were included. The results showed that, in younger individuals, the avoidant attachment dimension was associated both negatively and positively with activations in limbic regions, located at the level of Brodmann Area (BA) 13 (insula) and the medial globus pallidus and amygdala, while in older individuals, it was associated only negatively with sub-lobar activations in the caudate tail. Moreover, in younger individuals, the anxious attachment dimension was associated both negatively and positively with activations in several heterogeneous neural areas. Differently, in older individuals, the anxious attachment dimension showed only positive associations with neural activations, particularly in limbic regions, located at the level of BA 35 (parahippocampus) and 38 (temporal pole). These preliminary findings suggest potential differences in the neural correlates of insecure attachment according to age. It could be supposed that younger individuals have more flexible and less structured attachment-related regulatory strategies than older individuals, suggesting relevant clinical implications for attachment-based psychological interventions.
This scoping review examined neuroimaging evidence relating screen-based technology use to brain development in children aged 0-12 years. Nine studies were included. Most reported associations between higher screen exposure and less favorable neurodevelopmental outcomes, including reduced cortical thickness, lower gray and white matter integrity, decreased cerebellar volume, and altered connectivity in networks involved in language, attention, executive functioning, and emotional regulation. These neural differences were associated with poorer literacy and language skills, increased anxiety and depressive symptoms, and greater behavioral difficulties. Some evidence suggested positive effects from structured and interactive digital activities, particularly video gaming, which was linked to improvements in working memory, spatial awareness, fine motor performance, and increased regional brain volume. Findings indicate that the impact of screen-based technology is complex and may depend on the type, duration, and context of use. While excessive or unregulated screen exposure appears associated with less favorable developmental outcomes, targeted digital engagement may support specific cognitive functions. Further longitudinal and experimental research is needed to clarify causal pathways and guide evidence-based recommendations for children's digital media use.
The role of prior sleep, particularly nighttime sleep, in memory encoding is poorly understood in infants. The present study, therefore, focused on possible associations between nighttime sleep and memory encoding in the first year of life. First, the sleeping behavior of 6-month-old (n = 32) and 12-month-old (n = 35) infants was assessed for one night using actigraphy and sleep diaries. The following day, infants participated in a visual recognition memory task in the laboratory, which included photographs of female adults showing happy, angry, and neutral facial expressions. Six-month-old infants did not recognize any of the faces, whereas 12-month-old infants recognized the emotional, but not neutral faces, as indicated by novelty preference scores. Correlation and hierarchical regression analyses revealed that sleep efficiency and light sleep predicted novelty preference scores for angry and neutral faces in 6-month-olds, whereas light sleep and co-sleeping predicted novelty preference scores for angry faces in 12-month-olds. These results suggest that specific sleep parameters have distinct and age-specific significance for subsequent memory encoding.
Premature birth has long-term effects on sensory, motor, and cognitive development. Despite evidence of impaired motor function in young children born preterm, there is less known about motor learning and the characterization of the acquisition and retention of motor skills in this population. Furthermore, bimanual movements, important for performing everyday activities, may be preferentially affected in preterm children. In this study, we compared unimanual and bimanual motor skill learning in young children born preterm compared to children born at term age. Unimanual and bimanual de novo visuomotor learning tasks were implemented on a computerized tablet (Apple iPad). Fifty-five participants (N = 14 preterm), corrected age 5-8 years, completed three testing sessions: initial practice (72 practice attempts), 24-h retention (24 practice attempts), and 7-day retention (24 practice attempts). Speed (completion time) and accuracy (movement path length) characterized motor performance. Learning was determined by comparing performance at the end of initial practice to each retention test. Overall, preterm children exhibited reduced speed and accuracy on both tasks compared to term-born children. All children performed better on the unimanual version of the task. Retention was similar between groups and tasks. Biological age had a small, nonlinear relationship with performance. These results confirm that preterm children have impaired unimanual and bimanual skills but are capable of learning new visuomotor patterns, with potential differences in skill retention. This evidence provides insight into the varied trajectories of motor development of preterm children.
