Is Stress Reactivity an Intermediary Mechanism in the Association Between NR3C1 Methylation and Adolescent Loneliness?

Salivary glucocorticoid receptor gene DNA methylation and cortisol output in relation to lifestyle, psychological distress, and cognition in university students.

BACKGROUND University students often experience high psychosocial stress and lifestyle irregularities that may affect hypothalamic-pituitary-adrenal axis regulation and epigenetic regulation of the glucocorticoid receptor gene (NR3C1). This study examined associations of lifestyle factors with peripheral NR3C1 DNA methylation and cortisol output, and their relationships with psychological distress and cognitive function. METHODS A cross-sectional study included 97 university students (48 women; mean age = 21.6 years). Salivary NR3C1 promoter methylation was measured by pyrosequencing, and two components (C1, C2) were derived. Salivary cortisol area under the curve with respect to ground (AUCg) was calculated. Lifestyle behaviors, cardiorespiratory fitness (CRF), symptoms of depression, anxiety, and stress, and cognitive domains were assessed. Multiple regression and moderation analyses tested associations and interactions with sex and BMI. RESULTS In uncorrected analyses, higher sedentary behavior was associated with lower NR3C1 C2 scores, and higher physical activity and CRF were related to lower cortisol AUCg. Higher NR3C1 C1 scores were associated with poorer executive function and inhibition, and cortisol AUCg was positively associated with depressive symptoms. However, none of these associations survived correction for multiple comparisons. Exploratory analyses indicated that higher NR3C1 C2 scores were associated with better attention at lower BMI and better attention-processing speed in women, whereas higher NR3C1 C1 scores were associated with poorer inhibition in men. CONCLUSIONS Nominal findings suggest movement-related behaviors as the clearest lifestyle correlates of stress-system markers. Moderation analyses suggest sex- and BMI-related heterogeneity in selected cognition-methylation associations. These findings require confirmation in adequately powered studies.

Linking childhood adversity and daily hassles to adolescent sleep behaviors: Diurnal cortisol as a mediating pathway.

This study sought to examine whether diurnal cortisol served as an intermediary pathway linking childhood adversity and daily hassles to adolescent sleep behaviors (i.e., duration and quality). Data were drawn from 255 Chinese adolescents (32.2% female; Mage = 11.678 years, SD = 0.741, range = 10-14 years). Adolescents filled out a survey on demographics and childhood adversity at T1. One year later (T2), they completed 7-day reports on daily hassles and sleep behaviors and provided saliva samples for 3 consecutive days. Six months later (T3), adolescents completed a follow-up survey on their sleep behaviors. Multilevel structural equation models were conducted to examine the mediating effects of diurnal cortisol on associations between stressors and sleep duration and quality. Specific associations emerged between stressors and adolescent diurnal cortisol: Adolescents who reported greater childhood adversity at T1 exhibited a smaller cortisol awakening response (CAR) at T2; by contrast, on days when adolescents perceived more daily hassles, they exhibited a larger CAR the next day. For links between diurnal cortisol and sleep behaviors, distinct associations were observed for daily (within-person) versus longer term (between-person) effects. Finally, waking cortisol and CAR mediated the links between prior-day daily hassles and next-day sleep duration; the indirect effects of diurnal cortisol were not supported for the links between childhood adversity and sleep behaviors. Observing the temporal, time-lagged mechanism of diurnal cortisol explaining the links between daily stressors and sleep behaviors, this study points to important implications for practices on promoting adolescent sleep health. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

The Longitudinal Association Between Parent-Child Attachment and Adolescent Depressive Symptoms: Moderation by Oxytocin Receptor Polymorphisms

Maternal and paternal attachment may relate differently to adolescent depressive symptoms, but the potential contribution of oxytocin receptor (OXTR) gene single nucleotide polymorphisms (SNPs) to these associations remains unclear. This six-month longitudinal study included 746 seventh- and tenth-grade students (50.7% female) from Guangzhou, China. Parent-child attachment and saliva samples for genotyping were collected at baseline, and depressive symptoms were assessed at follow-up using the CES-D-10. Overall, 48.8% of adolescents screened positive for depressive symptoms. Compared with adolescents below the cutoff, those who screened positive reported lower parental trust/communication and higher alienation (all p < 0.01). In adjusted linear regression models, father-child trust/communication was negatively associated with subsequent depressive symptoms (β = −0.26, p < 0.01), whereas mother-child alienation was positively associated with subsequent depressive symptoms (β = 0.15, p = 0.02). Exploratory moderation analyses showed a nominal rs2254295 × mother-child alienation interaction before correction (β = −0.07, p = 0.046), but this effect did not survive FDR correction. Father-child trust/communication and mother-child alienation showed distinct associations with adolescent depressive symptoms. The possible moderating role of OXTR rs2254295 should be regarded as preliminary and requires replication in larger independent samples.

The interactive role of physiological reactivity and victimization responses on internalizing symptoms in early childhood.

The present short-term longitudinal study examined the associations between preschoolers' coping responses to their personal experience of peer victimization and later internalizing symptoms. This study prospectively tested autonomic nervous system reactivity (i.e., respiratory sinus arrhythmia reactivity, RSA-R; and skin conductance level reactivity, SCL-R) as moderators of these associations. This secondary data analysis assessed a relatively well-resourced sample of 83 preschoolers (M = 45.59 months old, SD = 3.80, 47.0% female) over the course of approximately 1 year: first during the spring of participants' preschool (Time 1) and again during the spring of the subsequent pre-kindergarten year (Time 2). Hypotheses were guided by polyvagal theory, which highlights the importance of interactive effects of the sympathetic and parasympathetic nervous systems in the stress response. Results demonstrated that approach coping was associated with decreases in later internalizing symptoms. In addition, avoidance coping was associated with decreases in internalizing symptoms for participants exhibiting SCL-R inhibition. RSA-R did not moderate associations between coping and later internalizing symptoms. These findings provide preliminary support for the hypothesis that the adaptive alignment between coping behaviors and physiological reactivity may serve as a protective factor in buffering against psychological distress.

association of BDNF Val66Met polymorphism with hPa and saM axis reactivity to psychological and physical stress

Sex-specific mechanisms of childhood trauma-related HPA axis dysregulation: Insights across four regulatory probes.

Blunted cortisol reactivity (BCR) to stress has been linked to trauma symptoms and early life adversity (ELA). Despite evidence for sex differences in ELA's impact on cortisol reactivity, few stress reactivity studies adequately assess sex-specificity. Further, most have measured salivary cortisol response to a single regulatory probe, limiting conclusions regarding mechanisms contributing to trauma-related HPA axis dysregulation. Using measures of cortisol binding globulin (CBG), serum adrenocorticotropic hormone (ACTH), and serum and salivary cortisol across four regulatory probes, this study assessed sex-specific mechanisms of ELA-related HPA axis dysregulation. 116 adults (55 female; 61 male) completed the Trier Social Stress Test (TSST), ACTH stimulation test, and low and high dose dexamethasone suppression tests (DST), and provided serum ACTH and cortisol, salivary cortisol, and CBG samples. For women, probes were scheduled to avoid ovulatory estrogen surges. Regressions in sex-disaggregated data examined the impact of ELA on cortisol reactivity and three candidate mechanisms of BCR. We found a negative association between salivary cortisol reactivity and ELA in females (p = .037), with no relation in males. In females, neither CBG nor adrenal sensitivity explained blunting; ELA was, however, associated with enhanced feedback inhibition (p = .033). Findings imply that the relation between ELA and adult BCR may primarily be present in females. The observed patterns were more consistent with enhanced feedback inhibition as a candidate pathway to trauma-related blunting in women than altered adrenal sensitivity or blunting explained by CBG. Future sex-disaggregated approaches may clarify persistently elusive pathways between trauma, HPA axis dysregulation, and adverse health outcomes.