The association between pubertal timing and diurnal cortisol activity in middle adolescence

Adverse childhood experiences and prospective changes in diurnal cortisol activity during the transition to adolescence: Moderation by daily coping and adolescent sex.

PURPOSE Examining circadian hypothalamic-pituitary-adrenal (HPA) axis activity during adolescence is vital for understanding physiological changes. Limited research explores risk and protective factors for diurnal HPA activity. This study investigates how adverse childhood experiences (ACEs) and coping are associated with changes in diurnal cortisol patterns, using a combination of physiological biomarkers (i.e., salivary cortisol), daily diaries, and longitudinal assessments spanning two years. METHODS The sample included 316 Chinese adolescents (33% females; T1 Mage = 10.79 years, SD = 0.84). At T1, adolescents reported ACEs, completed 7-day diaries on coping, and provided saliva samples for three consecutive days. Two years later (T2), adolescents completed a follow-up assessment on diurnal cortisol activity. Latent change score modeling was conducted to investigate changing patterns in diurnal cortisol and associations of ACEs and coping with the changing patterns. RESULTS From T1 to T2, waking cortisol decreased, CAR increased, and diurnal cortisol slopes became steeper. ACEs were associated with initial levels of diurnal cortisol activity but not changes in it: more ACEs were linked to higher T1 waking cortisol and a smaller T1 CAR. Higher ACEs were also associated with later wake-up times; later wake-up was associated with lower T1 CAR, more blunted T1 diurnal slopes, and flatter diurnal slopes across time. Daily coping (mean and variability) moderated the associations between ACEs and diurnal cortisol. CONCLUSION By observing coping as a moderator between ACEs and cortisol patterns, this study demonstrates that associations between ACEs and diurnal cortisol differ across adolescents' coping use and coping variability.

Functional brain network correlates of pubertal timing and depressive symptoms in preadolescence.

Association between menstrual cycle characteristics and mental health in early adolescence.

Adolescence marks a critical window for the emergence of mental health problems and reproductive maturation. Menstrual cycle characteristics - including pubertal timing, cycle regularity, menstrual pain, and premenstrual symptoms -may capture biological and experiential processes relevant to psychopathology. However, evidence linking menstrual features to a broad range of mental health outcomes, including ADHD symptoms, remains limited. Using data from the Adolescent Brain Cognitive Development (ABCD) Study (v6.1 N = 5,678 biological females; 17,567 post-menarche observations across 7 waves), we examined associations between reproductive timing, menstrual characteristics and symptoms of attention-deficit/hyperactivity disorder (ADHD), depression, and anxiety symptoms across repeated assessments in early adolescence using linear mixed-effects models with crossed random intercepts for site, family, and participant. Two co-primary model specifications were used: without BMI (M1, full sample) and with BMI (M2). False discovery rate correction was applied across outcomes. Earlier age at menarche was specifically associated with higher depression symptom scores (B = -0.087, pFDR < 0.001), with attenuation after BMI adjustment. Greater gynaecologic age (time since menarche TSM) also associated with higher depression scores (B = + 0.118, pFDR < 0.001) independent of chronological age and pubertal timing. Among girls with established cycles (TSM ≥ 2 years), irregular cycles were associated with higher depression and anxiety, whereas associations with ADHD did not remain after BMI adjustment. Long cycles were associated with anxiety only. Severe menstrual pain and premenstrual symptom severity showed dose-response associations with depression, anxiety, and ADHD that were robust to BMI adjustment. The association between irregular cycles and depression, and between long cycles and depression and anxiety, strengthened significantly with increasing gynaecologic age, while symptom burden associations were consistent throughout the post-menarcheal period. Menstrual symptom burden particularly severe pain and premenstrual distress and earlier menarche were consistently associated with higher levels of psychiatric symptoms in adolescent girls. These findings highlight menstrual health as a potentially informative dimension of adolescent mental health assessment. When girls present with significant menstrual symptoms, assessment of emotional wellbeing may be warranted.

Adrenal androgen mediates the association between obesity and accelerated skeletal maturation in children and adolescents

Childhood obesity is associated with advanced bone age (BA), but the underlying endocrine mechanisms remain unclear. We investigated the mediating role of dehydroepiandrosterone sulfate (DHEA-S) in the relationship between adiposity and skeletal maturation. This retrospective study included 1,252 children aged 4–12 years from a single center. Skeletal maturation was assessed using the BA-to-chronological age (CA) ratio. Advanced maturation was defined as BA/CA > 1.1. Mediation analysis was performed to evaluate whether DHEA-S explains the association between BMI SDS and skeletal maturation. Body mass index standard deviation score (BMI SDS) and DHEA-S were independently associated with the BA/CA ratio (p < 0.05). In boys younger than 9 years, DHEA-S demonstrated good discriminative performance for advanced maturation (Area under the curve = 0.817). Mediation analysis showed that DHEA-S significantly mediated the association between BMI and BA/CA in boys < 9 years (β = 0.512, p = 0.024) and in girls ≥ 8 years (β = 0.377, p = 0.003). In young boys, the direct effect of BMI became non-significant after inclusion of DHEA-S, consistent with substantial mediation by adrenal androgens. Adrenal androgen activity, reflected by DHEA-S, represents a significant endocrine pathway linking obesity to accelerated skeletal maturation. The magnitude of this mediation varies by age and sex, highlighting developmentally specific windows of endocrine-metabolic interaction in growing children.

Exploratory Biological Correlates of Cognitive and Language Performance in Healthy Pubertal Children: A Retrospective Cross-Sectional Study

Background/Objectives: Adolescence is a dynamic neurodevelopmental period during which structured language performance may reflect ongoing biological reorganization processes. This study examined whether inflammatory, nutritional, and hormonal biomarkers were modestly associated with structured language task performance and cognitive performance in healthy pubertal children. Methods: A total of 156 healthy pubertal children (78 female, 78 male; mean age of 11.84 ± 2.98 years) meeting Tanner Stage ≥ 2 were included in this retrospective cross-sectional study. Language was assessed with the Test of Language Development-Primary: Fourth Edition (TOLD-P:4; Turkish adaptation) and cognition with the Wechsler Intelligence Scale for Children-Revised (WISC-R). Pan-Immune-Inflammation Value (PIV), Prognostic Nutritional Index (PNI), Neutrophil-to-Lymphocyte Ratio (NLR), vitamin B12, 25-OH vitamin D, ferritin, and TSH were included as biomarkers. Two-block hierarchical OLS regression and Spearman correlations with Benjamini–Hochberg FDR correction were used. Results: The biomarker block provided a statistically significant incremental contribution to the spoken language model (ΔR2 = 0.066, p = 0.041; full model R2 = 0.287). The primary test statistic was ΔR2. In exploratory coefficient-level analyses that were not corrected for multiple comparisons, the PIV (β = +0.17, p = 0.033) and TSH (β = −0.17, p = 0.031) coefficients reached nominal significance. After FDR correction, PIV was positively associated with WISC-R Verbal score (ρ = +0.24, p_FDR = 0.019) and TSH negatively with TOLD-P:4 Speaking (ρ = −0.22, p_FDR = 0.029). Biomarker contribution to WISC-R Full-Scale IQ was non-significant (ΔR2 = 0.049, p = 0.223). Conclusions: At the block level, the biomarker set contributed significantly to the structured spoken-language model but not to the Full-Scale IQ model; however, one of the two FDR-significant bivariate associations involved a verbal cognitive measure (PIV with WISC-R Verbal). Any language-versus-cognition contrast should therefore be interpreted cautiously. The modest effect sizes suggest these relationships are best interpreted within a developmental and neuroimmune framework. Longitudinal and multimodal studies are needed to replicate these findings. Because the TOLD-P:4/TODİL was applied beyond its validated age range (4; 0–8; 11) and its cross-age scoring could not be verified from the retrospective records, all language-based findings are exploratory and require confirmation with an age-validated instrument; the study’s confirmatory finding is the FDR-significant association of PIV with age-appropriate WISC-R Verbal performance. Because the TOLD-P:4/TODİL composite scores could not be verified as comparable across the sample’s age range, all TOLD-P:4-based results reported here are exploratory and hypothesis-generating; the confirmatory analyses rely on the age-appropriate WISC-R outcomes.

Sex-specific associations between pubertal development and MASLD in children: evidence from the PROC study.