DHEA Moderates the Impact of Childhood Trauma on the HPA Axis in Adolescence.

BACKGROUND: Trauma can lead to long-term downregulation of the hypothalamic pituitary adrenal (HPA) axis. However, dehydroepiandrosterone (DHEA) has neuroprotective effects that may reduce the need for downregulation of the axis in response to stress. Furthermore, high DHEA/cortisol ratios are often conceptualized as better markers of DHEA's availability than DHEA alone, as ratios account for the coupling of DHEA and cortisol in response to stress. OBJECTIVES: In this study, we explored if DHEA and DHEA/cortisol ratios moderated the association between childhood maltreatment and the HPA axis stress response. METHODS: The sample consisted of 101 adolescents (ages 12-16) who completed the Child Trauma Questionnaire (CTQ) and the Trier Social Stress Test (TSST). Cortisol was modeled using saliva samples at 8 time points throughout the TSST. Cortisol and DHEA ratios were examined at baseline and 35 min after stress initiation. RESULTS: Childhood maltreatment was associated with less steep cortisol activation slope and peak cortisol levels, but DHEA and DHEA/cortisol ratios moderated this effect. At high levels of DHEA, the impact of childhood maltreatment on cortisol peak levels was no longer significant. In contrast, high DHEA/cortisol ratios were associated with an intensification of the impact of childhood maltreatment on peak levels. CONCLUSIONS: Results suggest that DHEA can limit the blunting of the HPA axis in response to childhood maltreatment. However, this protective effect was not reflected in high DHEA/cortisol ratios as predicted. Therefore, high DHEA and high DHEA/cortisol ratios may reflect different, and potentially opposite, processes.

Early trauma moderates the link between familial risk for depression and post-stress DHEA/cortisol ratios in adolescents.

BACKGROUND: One proposed mechanism for familial transmission of depression risk is impaired ability to regulate stress. While much of this work has focused on the stress hormone cortisol, there is evidence that the neuroprotective hormone dehydroepiandrosterone (DHEA) may play a critical role in stress regulation and that the ratios of DHEA to cortisol may provide meaningful information about individual differences in stress processing. In this study, we examined DHEA and DHEA/cortisol ratios among teens at low and high risk for depression. METHODS: Participants included 101 youth (12-16-year-old; 50 female) including 53 with a family history of depression (High Risk for depression). Adolescents and their parents completed diagnostic interviews, the Childhood Trauma Questionnaire and the Childhood Depression Inventory. Saliva samples were collected at multiple time points before and after adolescents underwent the Trier Social Stress Test. Cortisol and DHEA ratios were examined at baseline and 35 min post-stress initiation. RESULTS: High risk (HR) and low risk (LR) participants did not differ on DHEA/cortisol ratios. However, childhood trauma moderated the relationship between risk group and DHEA/cortisol ratios, where at high levels of trauma, HR participants had significantly higher ratios than LR participants. CONCLUSION: Our findings suggest that higher DHEA/cortisol ratios may not be indicative of greater protection against risk for depression as previously conceptualized. In the context of early trauma, higher DHEA/cortisol ratios may reflect a blunting of the HPA-axis that is not observed when examining cortisol levels alone. This study has implications for our conceptualization of DHEA/cortisol ratios as an indicator of risk for psychopathology.

HPA-Axis Activation as a Key Moderator of Childhood Trauma Exposure and Adolescent Mental Health.

Individual differences in a child's sensitivity to stress may influence whether youth exposed to trauma develop symptoms of psychopathology. We examined the interaction between HPA-axis reactivity to an acute stressor and exposure to different types of childhood trauma as predictors of mental health symptoms in a sample of youth. Youth (n = 121, ages 9-16; 47% female) completed a standardized stress task, including 5 post-stress salivary cortisol samples. Parents also completed the Child Behavior Checklist as a measure of child internalizing and externalizing symptoms in the past month, and completed the Early Trauma Inventory (ETI) as a measure of their child's trauma exposure. More emotional abuse and non-intentional trauma were associated with greater internalizing symptoms. Youth exposed to physical abuse who demonstrated slower HPA-axis reactivity had elevated internalizing and externalizing symptoms. Youth exposed to emotional abuse or non-intentional traumatic events who demonstrated faster HPA-axis reactivity had elevated internalizing and externalizing symptoms. Profiles of exaggerated or attenuated HPA-axis reactivity to acute stress may be risk factors for psychopathology in children facing different stressful social environments.

Age of Trauma Onset and HPA Axis Dysregulation Among Trauma-Exposed Youth.

The hypothalamic-pituitary-adrenal axis (HPA axis) is a pathway through which childhood trauma may increase risk for negative health outcomes. The HPA axis is sensitive to stress throughout development; however, few studies have examined whether timing of exposure to childhood trauma is related to differences in later HPA axis functioning. Therefore, we examined the association between age of first trauma and HPA axis functioning among adolescents, and whether these associations varied by sex. Parents of 97 youth (aged 9-16 years) completed the Early Trauma Inventory (ETI), and youth completed the Socially-Evaluated Cold-Pressor Task (SECPT). We measured salivary cortisol response to the SECPT, the cortisol awakening response, and diurnal regulation at home across 2 consecutive weekdays. Exposure to trauma during infancy related to delayed cortisol recovery from peak responses to acute stress, d = 0.23 to 0.42. Timing of trauma exposure related to diverging patterns of diurnal cortisol regulation for males, d = 0.55, and females, d = 0.57. Therefore, the HPA axis may be susceptible to developing acute stress dysregulation when exposed to trauma during infancy, whereas the consequences within circadian cortisol regulation may occur in the context of later trauma exposure and vary by sex. Further investigations are warranted to characterize HPA axis sensitivity to exposure to childhood trauma across child development.

Differential associations between childhood trauma subtypes and adolescent HPA-axis functioning.

UNLABELLED: Studies examining the association between childhood trauma exposure and neuroendocrine functioning have returned inconsistent findings. To date, few studies have accounted for the role exposure to different types of childhood trauma may have on different neuroendocrine adaptations, and no study has examined this association using multiple indices of hypothalamic-pituitary-adrenal axis (HPA-axis) functioning. The purpose of this study was to characterize the unique associations between exposure to physical abuse, emotional abuse, and non-intentional trauma, and multiple indices of HPA-axis functioning. METHODS: A community sample of 138 youth (aged 9-16) completed the Socially Evaluated Cold Pressor Task (SE-CPT) while their parents completed the Early Trauma Inventory (ETI). All youth then collected 4 diurnal salivary cortisol samples at home across 2 consecutive weekdays. RESULTS: High reported exposure to non-intentional trauma was associated with intact diurnal regulation but elevated cortisol at bedtime, physical abuse was associated with faster reactivity to acute stress, and emotional abuse was associated with delayed recovery of cortisol following acute stress. Taken together, there was a heterogeneous relationship among different indices of HPA-axis functioning and trauma subtype. DISCUSSION: Different types of childhood trauma exposure are related to distinct anomalies in HPA-axis functioning. This study underscores the importance of research incorporating multiple indices of HPA-axis functioning to inform our understanding of the underlying neuroendocrine dysregulation that may later lead to stress-related psychopathology.