Associations of a metal mixture with iron status in U.S. adolescents: Evidence from the National Health and Nutrition Examination Survey.

Iron is needed for normal development in adolescence. Exposure to individual environmental metals (e.g., lead) has been associated with altered iron status in adolescence, but little is known about the cumulative associations of multiple metals with Fe status. We used data from the 2017-2018 National Health and Nutrition Examination Survey (NHANES) to examine associations between a metal mixture (lead, manganese, cadmium, selenium) and iron status in 588 U.S. adolescents (12-17 years). We estimated cumulative and interactive associations of the metal mixture with five iron status metrics using Bayesian Kernel Machine Regression (BKMR). Higher concentrations of manganese and cadmium were associated with lower log-transformed ferritin concentrations. Interactions were observed between manganese, cadmium, and lead for ferritin and the transferrin receptor, where iron status tended to be worse at higher concentrations of all metals. These results may reflect competition between environmental metals and iron for cellular uptake. Mixed metal exposures may alter normal iron function, which has implications for adolescent development.

Impact of metabolic syndrome and its components on bone remodeling in adolescents.

INTRODUCTION: Osteoporosis and metabolic syndrome (MetS) are diseases that have serious public health consequences, reducing the quality of life of patients and increasing morbidity and mortality, with substantial healthcare expenditures. OBJECTIVE: To evaluate the impact of MetS on bone mineral density (BMD) and biochemical markers of bone formation and resorption in adolescents with excess weight. METHOD: A descriptive and analytical cross-sectional study was performed that evaluated 271 adolescents of both sexes (10 to 16 years). From the total sample, 42 adolescents with excess weight and the presence of MetS (14%) were selected. A further 42 adolescents with excess weight and without MetS were chosen, matched for chronological age, bone age, and pubertal developmental criteria to those with MetS, for each sex. Anthropometric measurements, blood pressure collection, and biochemical tests were performed in all adolescents, as well as evaluation of BMD and the bone biomarkers osteocalcin (OC), bone alkaline phosphatase (BAP), and carboxy-terminal telopeptide (S-CTx). RESULTS: The adolescents with excess weight and MetS exhibited significantly lower transformed BMD and concentrations of BAP, OC, and S-CTx compared to the matched group, except for OC in boys. A negative and significant correlation was observed between total body BMD and BAP (r = -0.55568; p = 0.005), OC (r = -0.81760; p = < .000), and S-CTx (r = -0.53838; p = 0.011) in girls. CONCLUSION: Metabolic syndrome may be associated with reduced bone mineral density and biochemical markers of bone formation and resorption in adolescents with excess weight.

Widespread Positive Direct and Indirect Effects of Regular Physical Activity on the Developing Functional Connectome in Early Adolescence.

Adolescence is a period of profound but incompletely understood changes in the brain's neural circuitry (the connectome), which is vulnerable to risk factors such as unhealthy weight, but may be protected by positive factors such as regular physical activity. In 5955 children (median age = 120 months; 50.86% females) from the Adolescent Brain Cognitive Development (ABCD) cohort, we investigated direct and indirect (through impact on body mass index [BMI]) effects of physical activity on resting-state networks, the backbone of the functional connectome that ubiquitously affects cognitive function. We estimated significant positive effects of regular physical activity on network connectivity, efficiency, robustness and stability (P ≤ 0.01), and on local topologies of attention, somatomotor, frontoparietal, limbic, and default-mode networks (P < 0.05), which support extensive processes, from memory and executive control to emotional processing. In contrast, we estimated widespread negative BMI effects in the same network properties and brain regions (P < 0.05). Additional mediation analyses suggested that physical activity could also modulate network topologies leading to better control of food intake, appetite and satiety, and ultimately lower BMI. Thus, regular physical activity may have extensive positive effects on the development of the functional connectome, and may be critical for improving the detrimental effects of unhealthy weight on cognitive health.

The role of pre-pubertal training history on hippocampal neurotrophic factors and glucocorticoid receptor protein levels in adult male rats.

Neurotrophic factors play an integral role in hippocampal plasticity, and interaction with HPA axis components, especially glucocorticoid receptors (GR), can mediate the structural and functional changes. In the present work, we investigated the long-term effects of combined exercise training (CET) and voluntary physical activity in an enriched environment (EE) in the pre-pubertal period on hippocampal neurotrophic factors and GR. For this purpose, a longitudinal study was designed. After three weeks, all rats were kept in the standard cages without any interventions until adulthood. Western blot analysis revealed a significant increase in hippocampal BDNF and VEGF protein levels in both EE and CET groups (P < 0.001), along with an increase in GR protein levels. In addition, EE decreased serum corticosterone levels compared to CET (P < 0.05). Serum insulin-like growth factor-1 (IGF-1) levels did not demonstrate remarkable changes between groups. Training interventions during sensitive developmental periods may produce profound and long-lasting effects on the hippocampus, at least in part by interactive effects of neurotrophic factors cascades and GR.

Height and Extremity-Length Prediction for Healthy Children Using Age-Based Versus Peak Height Velocity Timing-Based Multipliers.

BACKGROUND: The age-based multiplier method described by Paley et al. markedly simplifies height and limb length predictions but may not adequately accommodate children's maturational differences. Multipliers can be derived relative to any maturity measure. This study compares Paley age-based multipliers with those based on peak height velocity (PHV) timing. METHODS: In a longitudinal cohort of healthy children (66 male and 70 female), actual adult heights and limb lengths were compared with the measurements predicted using the Paley multipliers and multipliers developed relative to PHV timing. The age-based multipliers (adult divided by current) in our series were compared with those reported by Paley et al. to ensure that there were no systematic differences between the series. Absolute differences between the actual and predicted adult heights and limb lengths and the standard deviations of those differences were compared between the 2 methods. RESULTS: The average age-based multipliers in our series were nearly identical to those reported by Paley et al. The differences between the predicted and actual adult values showed wide ranges when either the Paley or the PHV multipliers were used during infancy. The Paley method performed better than the PHV method throughout pre-growth-spurt childhood. The PHV-timing-derived multipliers became superior as children entered their growth spurt, whereas the performance of the age-based multipliers worsened. In adolescence, the maximum standard deviation for adult-height-prediction errors with use of the Paley multipliers occurred at the age of 13.5 years for boys and 11.5 years for girls and was 7.0 cm for boys and 5.6 cm for girls. For limb lengths, the maximum standard deviations occurred 6 months earlier and were 3.9 cm for boys and 3.2 cm for girls. The maximum standard deviation for the height prediction error with the age-based method occurred at the average time of PHV for the population. The PHV method became better than the Paley method just before growth-spurt initiation, at age 8 in girls and 11 in boys. CONCLUSIONS: The age-based multipliers described by Paley et al. are superior to PHV-timing-based multipliers prior to the adolescent growth spurt for predicting height. They become less predictive, with wide standard deviations, as children enter their growth spurts, and PHV-derived multipliers become superior. The Paley height multipliers should be used before the age of 8 years in girls and 11 years in boys. After this, PHV-derived multipliers are superior for height and limb length prediction. In practice, these predictions are currently made using skeletal maturity, which is closely related to PHV during adolescence.

Anti-Müllerian Hormone Levels in Adolescence in Relation to Long-term Follow-up for Presence of Polycystic Ovary Syndrome.

CONTEXT: Anti-Müllerian hormone (AMH) measured in adolescence as biomarker for prediction of adult polycystic ovary syndrome (PCOS) is doubtful but not substantiated. OBJECTIVE: To investigate whether serum AMH levels and other PCOS-associated features in adolescence can predict the presence of PCOS in adulthood. DESIGN AND SETTING: A long-term follow-up study based on a unique adolescent study on menstrual irregularities performed between 1990 and 1997. PARTICIPANTS AND INTERVENTIONS: AMH was assayed in 271 adolescent girls. Data on PCOS features were combined with AMH levels. In 160 of the 271 (59%) participants, we collected information in adulthood about their menstrual cycle pattern and presence of PCOS (features) by questionnaire 2 decades after the initial study. RESULTS: AMH was higher in adolescent girls with oligomenorrhea compared with girls with regular cycles, median (interquartile range): 4.6 (3.1-7.5) versus 2.6 (1.7-3.8) µg/L (P < 0.001). Women with PCOS in adulthood had a higher median adolescent AMH of 6.0 compared with 2.5 µg/L in the non-PCOS group (P < 0.001). AMH at adolescence showed an area under the receiver operating characteristic curve for PCOS in adulthood of 0.78. In adolescent girls with oligomenorrhea the proportion developing PCOS in adulthood was 22.5% (95% CI, 12.4-37.4) against 5.1% (95% CI, 2.1-12.0) in girls with a regular cycle (P = 0.005). Given adolescent oligomenorrhea, adding high AMH as factor to predict adult PCOS or adult oligomenorrhea was of no value. CONCLUSIONS: Adolescent AMH either alone or adjuvant to adolescent oligomenorrhea does not contribute as prognostic marker for PCOS in adulthood. Therefore, we do not recommend routine its use in clinical practice.

Developmental outcomes after early surgery for complex congenital heart disease: a systematic review and meta-analysis.

AIM: (1) To systematically review the literature on developmental outcomes from infancy to adolescence of children with complex congenital heart disease (CHD) who underwent early surgery; (2) to run a meta-regression analysis on the Bayley Scales of Infant Development, Second Edition Mental Developmental Index and Psychomotor Developmental Index (PDI) of infants up to 24 months and IQs of preschool-aged children to adolescents; (3) to assess associations between perioperative risk factors and outcomes. METHOD: We searched pertinent literature (January 1990 to January 2019) in PubMed, Embase, CINAHL, and PsycINFO. Selection criteria included infants with complex CHD who had primary surgery within the first 9 weeks of life. Methodological quality, including risk of bias and internal validity, were assessed. RESULTS: In total, 185 papers met the inclusion criteria; the 100 with high to moderate methodological quality were analysed in detail. Substantial heterogeneity in the group with CHD and in methodology existed. The outcome of infants with single-ventricle CHD was inferior to those with two-ventricle CHD (respectively: average scores for PDI 77 and 88; intelligence scores 92 and 98). Perioperative risk factors were inconsistently associated with developmental outcomes. INTERPRETATION: The literature on children undergoing surgery in early infancy suggests that infants with a single ventricle are at highest risk of adverse developmental outcomes.

Reconsidering the role of sex hormones in psychopathy development: Estrogen and psychopathy among male justice-involved youth.

Prominent theory suggests that factor one psychopathic traits may develop from increased input from hormones in the hypothalamic pituitary gonadal axis (HPG; i.e., testosterone) and decreased input from the hypothalamic pituitary adrenal axis (HPA; i.e., cortisol). Although there are extensive findings connecting low cortisol to psychopathy, less support has emerged for high levels of testosterone. This study examined whether incorporating the HPG hormone, estradiol, into this model would reveal relationships in line with theory: high levels of estradiol and testosterone in combination with low levels of cortisol would inform psychopathic traits. Baseline and reactive hormone levels were measured and compared to Psychopathy Checklist-Youth Version (PCL-YV) interviews among 66 male justice-involved youth (M age = 15.73) in a Southeastern juvenile detention center. The primary findings of this study were relationships between interacting HPA and HPG axis hormones with facet one and facet two psychopathic traits. Specifically, psychopathy total scores, interpersonal traits, and affective traits related to estradiol and testosterone reactivity, in that psychopathy scores were more likely with decreases in hormone reactivity (i.e., change in hormone level) following a stressor. Moreover, affective traits related to reactivity in all three hormones. These findings support inclusion of estradiol in neurobiological models of psychopathy and consideration of the individual components of psychopathy. This study adds to the growing body of research supporting interactions between variations in functioning of the HPA and HPG axes in relation to psychopathy.

Description, prediction and causation: Methodological challenges of studying child and adolescent development.

Scientific research can be categorized into: a) descriptive research, with the main goal to summarize characteristics of a group (or person); b) predictive research, with the main goal to forecast future outcomes that can be used for screening, selection, or monitoring; and c) explanatory research, with the main goal to understand the underlying causal mechanism, which can then be used to develop interventions. Since each goal requires different research methods in terms of design, operationalization, model building and evaluation, it should form an important basis for decisions on how to set up and execute a study. To determine the extent to which developmental research is motivated by each goal and how this aligns with the research designs that are used, we evaluated 100 publications from the Consortium on Individual Development (CID). This analysis shows that the match between research goal and research design is not always optimal. We discuss alternative techniques, which are not yet part of the developmental scientist's standard toolbox, but that may help bridge some of the lurking gaps that developmental scientists encounter between their research design and their research goal. These include unsupervised and supervised machine learning, directed acyclical graphs, Mendelian randomization, and target trials.

Effect of early determinants on adolescent fat-free mass: RPS cohort of São Luís - MA.

OBJECTIVE: To analyze the effects of early determinants on adolescent fat-free mass. METHODS: A cohort study with 579 adolescents evaluated at birth and adolescence in a birth cohort in São Luís, Maranhão. In the proposed model, estimated by structural equation modeling, socioeconomic status (SES) at birth, maternal age, pregestational body mass index (BMI), gestational smoking, gestational weight gain, type of delivery, gestational age, sex of the newborn, length and weight at birth, adolescent socioeconomic status, "neither study/nor work" generation, adolescent physical activity level and alcohol consumption were tested as early determinants of adolescent fat-free mass (FFM). RESULTS: A higher pregestational BMI resulted in higher FFM in adolescence (Standardized Coefficient, SC = 0.152; p < 0.001). Being female implied a lower FFM in adolescence (SC = -0.633; p < 0.001). The negative effect of gender on FFM was direct (SC = -0.523; p < 0.001), but there was an indirect negative effect via physical activity level (SC = -0.085; p < 0.001). Women were less active (p < 0.001). An increase of 0.5 kg (1 Standard Deviation, SD) in birth weight led to a gain of 0.25 kg/m2 (0.106 SD) in adolescent FFM index (p = 0.034). Not studying or working had a negative effect on the adolescent's FFM (SC = -0.106; p = 0.015). Elevation of 1 SD in the adolescent's physical activity level represented an increase of 0.5 kg/m2 (0.207 SD) in FFM index (p < 0.001). CONCLUSIONS: The early determinants with the greatest effects on adolescent FFM are gender, adolescent physical activity level, pregestational BMI, birth weight and belonging to the "neither-nor" generation.

Estudio del crecimiento de la estatura en una muestra de niños, niñas y adolescentes sanos de Córdoba, Argentina / Height growth study of healthy children and adolescents from Córdoba, Argentina

OBJETIVO: Describir el crecimiento en estatura, estimar la edad pico del estirón, la velocidad de crecimiento en dicho punto, la talla final adulta esperada y los patrones diferenciales en una muestra poblacional de ambos sexos. SUJETOS Y MÉTODO: Se realizó un estudio transversal recabando prospectivamente datos demográficos, clínicos y antropométricos en sujetos sanos de ambos sexos, entre 2015 y 2016. Se calcularon los percentiles para la estatura mediante el método LMS (sesgo, mediana y coeficiente de variabilidad) y luego se ajustaron dichos valores utilizando el modelo 1 de Preece-Baines. RESULTADOS: Se evaluaron 861 sujetos, edades 2 - 18 años, 377 varones y 484 mujeres. La edad estimada al pico del estirón (h0) fue de 13,6 años en los niños y de 11,0 años en las niñas, con una velocidad de crecimiento lineal en ese punto (V2) de 6,4 cm/año para ambos sexos. La estatura adulta media esperada (hj) se estimó en 173,7 cm en los chicos y en 160,0 cm en las chicas. CONCLUSIONES: El modelo 1 de Preece-Baines permitió estimar satisfactoriamente la edad pico del estirón, la velocidad de crecimiento en dicho punto y la talla final adulta esperada.

OBJECTIVE: Based on a sample of children and adolescents of both genders, our objective is to des cribe height growth, estimate the peak age at growth spurt, growth rate at this point, the final adult height expected, and differential patterns SUBJECTS AND METHOD: A cross-sectional study was conduc ted using demographic, clinical, and anthropometric data collected prospectively from children and adolescents of both sexes between 2015 and 2016. Height percentiles were calculated using the LMS (skewness, median, and coefficient of variation) method and then adjusted using the Preece-Baines model 1. RESULTS: We evaluated 861 participants (484 girls, 377 boys), aged between 2 and 18 years. The estimated peak age at growth spurt (he) was 13.6 years in boys and 11.0 years in girls, with a peak growth rate (V2) at this point of 6.4 cm/year for both sexes. The mean expected adult height (h1) was 173.7 cm in boys and 160.0 cm in girls. CONCLUSIONS: Preece-Baines model 1 provides satisfactory estimates for the peak age at growth spurt, peak growth rate at this point, and final expected adult height.

Bone Development in Transgender Adolescents Treated With GnRH Analogues and Subsequent Gender-Affirming Hormones.

CONTEXT: Hormonal interventions in adolescents with gender dysphoria may have adverse effects, such as reduced bone mineral accrual. OBJECTIVE: To describe bone mass development in adolescents with gender dysphoria treated with gonadotropin-releasing hormone analogues (GnRHa), subsequently combined with gender-affirming hormones. DESIGN: Observational prospective study. SUBJECTS: 51 transgirls and 70 transboys receiving GnRHa and 36 transgirls and 42 transboys receiving GnRHa and gender-affirming hormones, subdivided into early- and late-pubertal groups. MAIN OUTCOME MEASURES: Bone mineral apparent density (BMAD), age- and sex-specific BMAD z-scores, and serum bone markers. RESULTS: At the start of GnRHa treatment, mean areal bone mineral density (aBMD) and BMAD values were within the normal range in all groups. In transgirls, the mean z-scores were well below the population mean. During 2 years of GnRHa treatment, BMAD stabilized or showed a small decrease, whereas z-scores decreased in all groups. During 3 years of combined administration of GnRHa and gender-affirming hormones, a significant increase of BMAD was found. Z-scores normalized in transboys but remained below zero in transgirls. In transgirls and early pubertal transboys, all bone markers decreased during GnRHa treatment. CONCLUSIONS: BMAD z-scores decreased during GnRHa treatment and increased during gender-affirming hormone treatment. Transboys had normal z-scores at baseline and at the end of the study. However, transgirls had relatively low z-scores, both at baseline and after 3 years of estrogen treatment. It is currently unclear whether this results in adverse outcomes, such as increased fracture risk, in transgirls as they grow older.

Increased dehydroepiandrosterone (DHEA) is associated with anxiety in adolescent girls.

The pubertal period is a time of rapid increase in the incidence of anxiety disorders, and thus, pubertal hormones may play a role in the precipitation of anxious psychopathology. DHEA, a steroid hormone that surges in adolescence, has been previously linked to anxiety, although the direction of this effect has been mixed. Using a cross-sectional design in a sample of 286 adolescent girls, the present study examined associations between salivary DHEA concentrations and self-report and interview-based measures of anxiety while controlling for pubertal status, menarche status, assessment time of day, and other hormones including testosterone, estradiol, and progesterone. Increased salivary DHEA concentrations were associated with more self-reported anxiety symptoms, increased anxiety symptom counts based on clinical interview, and increased probability of an anxiety disorder. Out of all anxiety symptom domains examined, generalized anxiety disorder symptoms were the best predictor of salivary DHEA concentrations after controlling for pubertal development. Collectively, our findings suggest relevance for DHEA in the development of anxiety in the pubertal period, as well as a robust relationship between DHEA and emerging symptoms of pathological worry during adolescence. The present study underscores the importance of examining associations between DHEA concentrations and anxiety in longitudinal designs.

Pubertal timing predicts adult psychosexuality: Evidence from typically developing adults and adults with isolated GnRH deficiency.

Evidence suggests that psychosexuality in humans is modulated by both organizational effects of prenatal and peripubertal sex steroid hormones, and by activational effects of circulating hormones in adulthood. Experimental work in male rodents indicates that sensitivity to androgen-driven organization of sexual motivation decreases across the pubertal window, such that earlier puberty leads to greater sex-typicality. We test this hypothesis in typically developing men (n = 231) and women (n = 648), and in men (n = 72) and women (n = 32) with isolated GnRH deficiency (IGD), in whom the precise timing of peripubertal hormone exposure can be ascertained via the age at which hormone replacement therapy (HRT) was initiated. Psychosexuality was measured with the Sexual Desire Inventory-2 (SDI-2) and Sociosexual Orientation Inventory-Revised (SOI-R). In both sexes, earlier recalled absolute pubertal timing predicted higher psychosexuality in adulthood, although the magnitude of these associations varied with psychosexuality type and group (i.e., typically developing and IGD). Results were robust when controlling for circulating steroid hormones in typically developing participants. Age of initiation of HRT in men with IGD negatively predicted SOI-R. We discuss the clinical implications of our findings for conditions in which pubertal timing is medically altered.

Pubertal Development: What's Normal/What's Not.

Onset of puberty, as defined by breast stage 2, appears to be starting at younger ages since the 1940s. There is an ongoing controversy regarding what is normative, as well as what is normal, and the evaluation that is deemed necessary for girls maturing before 8 years of age. There are potential implications of earlier pubertal timing, including psychosocial consequences during adolescence, as well as longer term risks, such as breast cancer and cardiometabolic risks. There are additional consequences derived from slower pubertal tempo, for age of menarche has not decreased as much as age of breast development; these include longer interval between sexual initiation and intentional childbearing, as well as a broadened window of susceptibility to endocrine-related cancers.

Gendered Pathways of Internalizing Problems from Early Childhood to Adolescence and Associated Adolescent Outcomes.

Despite trends indicating worsening internalizing problems, characterized by anxiety and depression, there is dearth of research examining gender differences in developmental trajectories of internalizing problems from early childhood to adolescence. Drawing on the UK Millennium Cohort Study (n = 17,206, 49% female), this study examines trajectories of parent-reported, clinically-meaningful (reflecting the top 10%) internalizing problems from ages 3 to 14 years and their early predictors and adolescent outcomes. Group-based modelling revealed three trajectories when examining boys and girls together, but there were significant gender differences. When examining boys and girls separately, four trajectories were identified including two relatively stable trajectories showing either high or low probabilities of internalizing problems. An increasing trajectory was also found for both boys and girls, showing an increasing probability of internalizing problems which continued to rise for girls, but levelled off for boys from age 11. A decreasing trajectory was revealed for boys, while a moderate but stable trajectory was identified for girls. Boys and girls in the increasing and high probability groups were more likely to report a number of problematic outcomes including high BMI, self-harm, low mental wellbeing, depressive symptoms, and low educational motivation than the low group. Girls on the increasing trajectory also reported more cigarette and cannabis use and early sexual activity at age 14 compared to girls on the low trajectory. Findings suggest that intervention strategies take a systemic view, targeting not only internal feelings, but also behaviours potentially associated with later negative outcomes.

Effect of early determinants on adolescent fat-free mass: RPS cohort of São Luís - MA

ABSTRACT OBJECTIVE: To analyze the effects of early determinants on adolescent fat-free mass. METHODS: A cohort study with 579 adolescents evaluated at birth and adolescence in a birth cohort in São Luís, Maranhão. In the proposed model, estimated by structural equation modeling, socioeconomic status (SES) at birth, maternal age, pregestational body mass index (BMI), gestational smoking, gestational weight gain, type of delivery, gestational age, sex of the newborn, length and weight at birth, adolescent socioeconomic status, "neither study/nor work" generation, adolescent physical activity level and alcohol consumption were tested as early determinants of adolescent fat-free mass (FFM). RESULTS: A higher pregestational BMI resulted in higher FFM in adolescence (Standardized Coefficient, SC = 0.152; p < 0.001). Being female implied a lower FFM in adolescence (SC = −0.633; p < 0.001). The negative effect of gender on FFM was direct (SC = −0.523; p < 0.001), but there was an indirect negative effect via physical activity level (SC = −0.085; p < 0.001). Women were less active (p < 0.001). An increase of 0.5 kg (1 Standard Deviation, SD) in birth weight led to a gain of 0.25 kg/m2 (0.106 SD) in adolescent FFM index (p = 0.034). Not studying or working had a negative effect on the adolescent's FFM (SC = −0.106; p = 0.015). Elevation of 1 SD in the adolescent's physical activity level represented an increase of 0.5 kg/m2 (0.207 SD) in FFM index (p < 0.001). CONCLUSIONS: The early determinants with the greatest effects on adolescent FFM are gender, adolescent physical activity level, pregestational BMI, birth weight and belonging to the "neither-nor" generation.

Facial emotion recognition in children treated for posterior fossa tumours and typically developing children: A divergence of predictors.

Facial emotion recognition (FER) deficits are evident and pervasive across neurodevelopmental, psychiatric, and acquired brain disorders in children, including children treated for brain tumours. Such deficits are thought to perpetuate challenges with social relationships and decrease quality of life. The present study combined eye-tracking, neuroimaging and cognitive assessments to evaluate if visual attention, brain structure, and general cognitive function contribute to FER in children treated for posterior fossa (PF) tumours (patients: n = 36) and typically developing children (controls: n = 18). To assess FER, all participants completed the Diagnostic Analysis of Nonverbal Accuracy (DANVA2), a computerized task that measures FER using photographs, while their eye-movements were recorded. Patients made more FER errors than controls (p < .01). Although we detected subtle deficits in visual attention and general cognitive function in patients, we found no associations with FER. Compared to controls, patients had evidence of white matter (WM) damage, (i.e., lower fractional anisotropy [FA] and higher radial diffusivity [RD]), in multiple regions throughout the brain (all p < .05), but not in specific WM tracts associated with FER. Despite the distributed WM differences between groups, WM predicted FER in controls only. In patients, factors associated with their disease and treatment predicted FER. Our study provides insight into predictors of FER that may be unique to children treated for PF tumours, and highlights a divergence in associations between brain structure and behavioural outcomes in clinical and typically developing populations; a concept that may be broadly applicable to other neurodevelopmental and clinical populations that experience FER deficits.

Immature excitatory neurons develop during adolescence in the human amygdala.

The human amygdala grows during childhood, and its abnormal development is linked to mood disorders. The primate amygdala contains a large population of immature neurons in the paralaminar nuclei (PL), suggesting protracted development and possibly neurogenesis. Here we studied human PL development from embryonic stages to adulthood. The PL develops next to the caudal ganglionic eminence, which generates inhibitory interneurons, yet most PL neurons express excitatory markers. In children, most PL cells are immature (DCX+PSA-NCAM+), and during adolescence many transition into mature (TBR1+VGLUT2+) neurons. Immature PL neurons persist into old age, yet local progenitor proliferation sharply decreases in infants. Using single nuclei RNA sequencing, we identify the transcriptional profile of immature excitatory neurons in the human amygdala between 4-15 years. We conclude that the human PL contains excitatory neurons that remain immature for decades, a possible substrate for persistent plasticity at the interface of the hippocampus and amygdala.