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.
Early (before age 6) potentially traumatic events (PTEs) may interact with hypothalamic-pituitary-adrenal (HPA) axis functioning to shape outcomes involving externalizing problems and anxiety. However, directions of effects remain unclear. This study examined associations between aspects of HPA axis reactivity, anxiety, and externalizing problems over two years by early PTE exposure history, while statistically capturing the co-occurrence of symptom domains. Youth (N = 189; Mage = 10.96 years, SD = 2.51, Range = 8-15; 52.4% female, 47.1% male; 50.3% White, 35.4% Black/African American, 6.4% Other; 7.4% Hispanic/Latine) were included if they had early PTE exposure (n = 107) or had never experienced a PTE (n = 82). HPA axis reactivity to social stress was calculated using area under the curve with respect to ground (AUCg) and increase (AUCi). For youth with early PTE exposure, higher AUCg was concurrently associated with more externalizing symptoms and greater predominance of externalizing over anxiety. Blunted AUCi predicted increasing predominance of externalizing for the early PTE group, but elevated AUCi predicted increases in anxiety for the no PTE group. Findings highlight distinct roles of overall and reactive HPA axis functioning in shaping outcomes following early trauma.
Gretchen R. Perhamus, Rachel E. Siciliano, Tiffany Phu et al.· Development and Psychopathol...· 0 citations
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.
Mingjun Xie, Yijia Li, Yueqing Hu et al.· Psychoneuroendocrinology· 0 citations
This study examined whether saliva-derived DNA methylation in the glucocorticoid receptor (NR3C1) gene was linked to loneliness through dysregulation of the hypothalamic-pituitary-adrenal axis (HPA-axis) in 101 early adolescents (Mage = 11.61 years, SDage = 0.64, 55.45% girls). Using person-centered analyses to account for interindividual differences in adolescents' stress reactivity, we identified three subgroups of cortisol responders to a social evaluative stressor: A hyporesponsive subgroup (30.5%), a moderate-responsive subgroup (44.2%), and a hyperresponsive subgroup (25.3%). Exploratory analyses also identified subgroups for two markers of the autonomous nervous system (ANS), that is, heart rate (HR) and skin conductance (SC). Furthermore, the indirect effects from NR3C1 methylation to early adolescent loneliness via individual differences in stress responses were examined. Results indicated that higher NR3C1 methylation levels were associated with a lower probability of belonging to the most reactive stress response subgroups for cortisol and HR, and to the high mean-level subgroup for SC. Additionally, higher probabilities of belonging to the low mean-level SC subgroup were associated with higher levels of loneliness. However, there was no evidence that NR3C1 methylation was associated with early adolescent loneliness, either directly or indirectly via stress reactivity. These findings highlight significant individual differences in stress reactivity, emphasizing the need to explicitly consider such variability in future research. Moreover, the results suggest that NR3C1 methylation is linked to individual differences in stress responding, warranting further investigation.
Yentl Koopmans, S. Nelemans, Patricia Bijttebier et al.· Developmental Psychobiology· 0 citations
Findings suggest that more severe stressors related to health/mental health may be more salient for early development of the hypothalamic-pituitary-adrenal system than less severe stressors (e.g., moving).
Yu Chen, E. Leerkes, Cheryl Buehler et al.· Infant Behavior and Developm...· 0 citations
Nonlinear interactions between cortisol indices and daily stressor severity appear to predict 9-year alcohol use disorder and substance use disorder severity, with cortisol area under the curve emerging as the most robust indicator.
N. Zainal, Natalia Van Doren· Addiction· 0 citations
This work emphasizes the necessity of considering sex when investigating developmental and neurobiological underpinnings of stress-related disorders and displays a vast range of lasting effects of developmental stress on the brain, which provides a valuable resource for future studies aiming to improve psychiatric treatments.
S. Narayan, C. Beer, V. Kovářová et al.· Proceedings of the National...· 0 citations
