Neurocognitive Profile in Pediatric Kidney Transplant Candidates: Effects of Medical and Sociodemographic Factors.

Background: We evaluated the effects of kidney failure etiology, dialysis, and sociodemographic factors on the subdomains of intellectual functioning in pediatric kidney transplant candidates. Methods: This retrospective study included 78 pediatric kidney transplant candidates who completed a Wechsler Intelligence Scale assessment during pre-transplant neuropsychological evaluation between 1/1/2010 and 10/31/2022. Linear regression models were employed to examine the effects of kidney failure etiology, dialysis status, neighborhood area deprivation, and race on subdomains of intellectual functioning. Results: The mean scores of various intellectual functioning domains in pediatric kidney transplant candidates were significantly lower than in the general population (ps <0.001). After adjusting for covariates, patients with congenital anomalies of the kidney and urinary tract had significantly lower processing speed (M=85; 95% CI: 79-91) compared to patients with nephrotic syndrome (M=99; 95% CI: 90-107) and other etiologies (M=84; 95% CI: 78-90) (p=0.003). Patients living in high-level deprivation neighborhoods showed lower working memory performance (M=84, 95% CI: 77-91) than patients living in median-level (M=91, 95% CI: 87-95) and low-level (M=98, 95% CI: 92-104) neighborhood area deprivation (p=0.03). Patients from marginalized racial groups demonstrated lower verbal skills (M=80, 95% CI: 74-87) than White patients (M=92, 95% CI: 88-97) (p=0.02). Additionally, patients receiving dialysis showed higher reasoning skills (M=98, 95% CI: 90-104) than patients without dialysis (M= 90, 95% CI: 86-95) (p=0.04). Conclusions: Neurocognitive development in pediatric kidney transplant candidates is associated with medical and sociodemographic factors. Strategies to monitor, treat, and accommodate neurocognitive concerns need to be considered to optimize long-term medical and social outcomes.

Neurodevelopmental profile of infants and toddlers awaiting a kidney transplant.

BACKGROUND: Infants and toddlers with kidney failure are susceptible to neurodevelopmental delays due to medical comorbidities and rapid brain development in early childhood. However, research on the neuropsychological development of this patient population has been limited over the past 10 years. METHODS: We performed a retrospective study to evaluate the neurodevelopmental functioning of infants/toddlers with kidney failure who completed the Bayley Scales of Infant and Toddler Development (3rd and 4th Edition) as part of a pretransplant evaluation between 2010 and 2022 (n = 23; Mage = 18 months, SD = 8.53; 16 males) using t-tests, linear model, and Pearson correlations. RESULTS: Mean Bayley scores of participants were below normative means for cognition (M = 86.74, 95% CI = 80.53-92.94, p < 0.001), language (M = 79.20, 95% CI = 73.32-85.08, p < 0.001), and motor (M = 78.00, 95% CI = 70.15-85.85, p < 0.001) domains. After adjusting for prematurity and epilepsy, patients on dialysis had significantly lower cognitive (78.7 vs. 93.8; p = 0.001) and motor scores (67.1 vs. 85.5; p = 0.01) compared to no dialysis. Pretransplant cognitive scores were positively correlated with posttransplant Full-Scale IQ (r(8) = 0.65 p = 0.04), verbal comprehension (r(8) = 0.75 p = 0.02), and fluid reasoning (r(7) = 0.68 p = 0.045). Similarly, pretransplant language scores were positively correlated with posttransplant Full-Scale IQ (r(7) = 0.74 p = 0.03) and verbal comprehension (r(7) = 0.73 p = 0.03). Of the 16 participants who reached age > 5 years during the study period, seven were diagnosed with a neurodevelopmental disorder, including three with autism spectrum disorder. CONCLUSIONS: Infants and toddlers with kidney failure are at risk of developmental delays and later neurodevelopmental disorders. Dialysis is associated with cognitive and motor delays independent of prematurity and epilepsy.

The Development of Stress Reactivity and Regulation in Children and Adolescents.

Adversity experienced in early life can have detrimental effects on physical and mental health. One pathway in which these effects occur is through the hypothalamic-pituitary-adrenal (HPA) axis, a key physiological stress-mediating system. In this review, we discuss the theoretical perspectives that guide stress reactivity and regulation research, the anatomy and physiology of the axis, developmental changes in the axis and its regulation, brain systems regulating stress, the role of genetic and epigenetics variation in axis development, sensitive periods in stress system calibration, the social regulation of stress (i.e., social buffering), and emerging research areas in the study of stress physiology and development. Understanding the development of stress reactivity and regulation is crucial for uncovering how early adverse experiences influence mental and physical health.

Perceptual learning is robust to manipulations of valence and arousal in childhood and adulthood.

Despite clear links between affective processes in many areas of cognition and perception, the influence of affective valence and arousal on low-level perceptual learning have remained largely unexplored. Such influences could have the potential to disrupt or enhance learning that would have long-term consequences for young learners. The current study manipulated 8- to 11-year-old children's and young adults' mood using video clips (to induce a positive mood) or a psychosocial stressor (to induce a negative mood). Each participant then completed one session of a low-level visual learning task (visual texture paradigm). Using novel computational methods, we did not observe evidence for the modulation of visual perceptual learning by manipulations of emotional arousal or valence in either children or adults. The majority of results supported a model of perceptual learning that is overwhelmingly constrained to the task itself and independent from external factors such as variations in learners' affect.

Infants' neural responses to emotional faces are related to maternal anxiety.

BACKGROUND: Postnatal maternal anxiety is common (estimates as high as 40% prevalence) and is associated with altered mother-infant interactions (e.g., reduced maternal emotional expression and engagement). Neural circuitry supporting infants' face and emotion processing develops in their first year. Thus, early exposure to maternal anxiety may impact infants' developing understanding of emotional displays. We examine whether maternal anxiety is associated with individual differences in typically developing infants' neural responses to emotional faces. METHODS: One hundred and forty two mother-infant dyads were assessed when infants were 5, 7, or 12 months old. Infants' electroencephalographic (EEG) data were recorded while passively viewing female happy, fearful, and angry faces. Three event-related potential (ERP) components, each linked to face and emotion processing, were evaluated: NC, N290, and P400. Infant ERP amplitude was related to concurrent maternal-report anxiety assessed with the Spielberger State-Trait Anxiety Inventory (Trait form). RESULTS: Greater maternal anxiety predicted more negative NC amplitude for happy and fearful faces in left and mid-central scalp regions, beyond covarying influences of maternal depression symptoms, infant negative emotionality, and infant age. CONCLUSIONS: Postnatal maternal anxiety is related to infants' neural processing of emotional expressions. Infants of mothers endorsing high trait anxiety may need additional attentional resources to process happy and fearful faces (expressions less likely experienced in mother-infant interactions). Future research should investigate mechanisms underlying this association, given possibilities include experiential, genetic, and prenatal factors.

Converging neural and behavioral evidence for a rapid, generalized response to threat-related facial expressions in 3-year-old children.

Electrophysiological studies on adults suggest that humans are efficient at detecting threat from facial information and tend to grant these signals a priority in access to attention, awareness, and action. The developmental origins of this bias are poorly understood, partly because few studies have examined the emergence of a generalized neural and behavioral response to distinct categories of threat in early childhood. We used event-related potential (ERP) and eye-tracking measures to examine children's early visual responses and overt attentional biases towards multiple exemplars of angry and fearful vs. other (e.g., happy and neutral) faces. A large group of children was assessed longitudinally in infancy (5, 7, or 12 months) and at 3 years of age. The final ERP dataset included 148 infants and 132 3-year-old children; and the final eye-tracking dataset included 272 infants and 334 3-year-olds. We demonstrate that 1) neural and behavioral responses to facial expressions converge on an enhanced response to fearful and angry faces at 3 years of age, with no differentiation between or bias towards one or the other of these expressions, and 2) a support vector machine learning model using data on the early-stage neural responses to threat reliably predicts the duration of overt attentional dwell time for threat-related faces at 3 years. However, we found little within-subject correlation between threat-bias attention in infancy and at 3 years of age. These results provide unique evidence for the early development of a rapid, unified response to two distinct categories of facial expressions with different physical characteristics, but shared threat-related meaning.

Atypical Emotional Electrodermal Activity in Toddlers with Autism Spectrum Disorder.

Past studies in autism spectrum disorder (ASD) indicate atypical peripheral physiological arousal. However, the conditions under which these atypicalities arise and their link with behavioral emotional expressions and core ASD symptoms remain uncertain. Given the importance of physiological arousal in affective, learning, and cognitive processes, the current study examined changes in skin conductance level (ΔSCL) in 41 toddlers with ASD (mean age: 22.7 months, SD: 2.9) and 32 age-matched toddlers with typical development (TD) (mean age: 21.6 months, SD: 3.6) in response to probes designed to induce anger, joy, and fear emotions. The magnitude of ΔSCL was comparable during anger (P = 0.206, d = 0.30) and joy (P = 0.996, d = 0.01) conditions, but significantly lower during the fear condition (P = 0.001, d = 0.83) in toddlers with ASD compared to TD peers. In the combined samples, ΔSCL positively correlated with intensity of behavioral emotional expressivity during the anger (r[71] = 0.36, P = 0.002) and fear (r[68] = 0.32, P = 0.007) conditions, but not in the joy (r[69] = -0.15, P = 0.226) condition. Finally, ΔSCL did not associate with autism symptom severity in any emotion-eliciting condition in the ASD group. Toddlers with ASD displayed attenuated ΔSCL to situations aimed at eliciting fear, which may forecast the emergence of highly prevalent internalizing and externalizing problems in this population. The study putatively identifies ΔSCL as a dimension not associated with severity of autism but with behavioral responses in negatively emotionally challenging events and provides support for the feasibility, validity, and incipient utility of examining ΔSCL in response to emotional challenges in very young children. LAY SUMMARY: Physiological arousal was measured in toddlers with autism exposed to frustrating, pleasant, and threatening tasks. Compared to typically developing peers, toddlers with autism showed comparable arousal responses to frustrating and pleasant events, but lower responses to threatening events. Importantly, physiological arousal and behavioral expressions were aligned during frustrating and threatening events, inviting exploration of physiological arousal to measure responses to emotional challenges. Furthermore, this study advances the understanding of precursors to emotional and behavioral problems common in older children with autism. Autism Res 2020, 13: 1476-1488. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

Patterns of change in telomere length over the first three years of life in healthy children.

There is growing interest in the use of telomere length as a biomarker of health and a predictor of later morbidity and mortality. However, little is known about developmentally expected telomere erosion over the first years of life. This gap hinders our ability to interpret the meaning of relative telomere length and rate of attrition in relation to risk factors and health outcomes. The overall goal of this study was to examine the rate of relative telomere length attrition in a large, normative sample of healthy children (N = 630) followed from infancy to three years of age. A secondary goal was to explore associations between sociodemographic characteristics and telomere erosion over this time period. Relative telomere length was assessed from DNA in saliva samples collected in infancy (M = 8.6 months), age 2 years (M = 25.2 months), and age 3 years (M = 38.3 months). In the sample as a whole, relative telomere length decreased from infancy to 2 years but remained stable from 2 years to 3 years. Notably, increases in relative telomere length were observed in 29 % of children between infancy and 2 years of age and in 46 % of children between 2 and 3 years of age; 62 % of children showed both increases and decreases in relative telomere length across the study period. Females showed longer relative telomere length than males, regardless of timepoint. There was some evidence that parental age and family finances were associated with changes in child relative telomere length across time. Overall, the findings suggest that telomere length attrition is not uniform across the early years of life, with the most rapid attrition occurring during the first two years, and that increases as well as decreases in telomere length during this period are commonly observed.

Emotional Expressivity in Toddlers With Autism Spectrum Disorder.

OBJECTIVE: There is a prevailing notion that children with autism spectrum disorder (ASD) exhibit intense negative and attenuated positive emotions, although the empirical evidence regarding their emotional expressiveness (EE) is limited. Given the importance of emotions in shaping social and cognitive development, we examined intensity and valence of EE and links between EE and autism severity and parent-reported temperament in ASD. METHOD: Toddlers (aged 21.2 months) with ASD (n = 43), developmental delay (DD, n = 16), and typical development (TD, n = 40) underwent standardized probes designed to induce anger, joy, and fear. Intensity of EE through facial and vocal channels were coded offline. Autism severity and temperament were quantified using the Autism Diagnostic Observation Schedule-2 (ADOS-2) and Early Childhood Behavior Questionnaire (ECBQ). RESULTS: The ASD group exhibited less intense fear compared to both the DD and TD groups, more intense anger than DD but not TD, with no differences in joy intensity. All groups showed similar levels of incongruous negative EE. Intensity of fear and anger were not associated with severity of autism symptoms, but lower intensity of joy was related to greater autism severity. Expressed fear and joy were associated with temperament. CONCLUSION: The study provides no support for a negative emotionality bias in ASD. Instead, toddlers with ASD display a muted response to threat and an accentuated response to goal blockage, whereas the ability to express positive emotions appears intact. Negative emotionality and social disability dimensions are independent. The study demonstrates the complexity of EE in ASD and motivates investigations into underlying mechanisms as well as its role in shaping complex phenotypes of affected children.