Linking the hemodynamic consequences of adverse childhood experiences to an altered HPA axis and acute stress response

2020 ◽  
Author(s):  
Kylie S. Dempster ◽  
Deborah D. O'Leary ◽  
Adam J. MacNeil ◽  
Gary J. Hodges ◽  
Terrance J. Wade
Keyword(s):  
Stress Response ◽  
Hpa Axis ◽  
Adverse Childhood Experiences ◽  
Acute Stress ◽  
Childhood Experiences ◽  
Adverse Childhood ◽  
Acute Stress Response

scholarly journals Adverse childhood experiences, daytime salivary cortisol, and depressive symptoms in early adulthood: a longitudinal genetically informed twin study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eleonora Iob ◽  
Jessie R. Baldwin ◽  
Robert Plomin ◽  
Andrew Steptoe
Keyword(s):  
Depressive Symptoms ◽  
Hpa Axis ◽  
Salivary Cortisol ◽  
Adverse Childhood Experiences ◽  
Emotional Abuse ◽  
Early Adulthood ◽  
Cumulative Exposure ◽  
Childhood Experiences ◽  
Adverse Childhood ◽  
Cortisol Levels

AbstractDysregulated hypothalamic–pituitary–adrenal (HPA)-axis function might underlie the relationship between adverse childhood experiences (ACEs) and depression. However, limited research has examined the possible mediating role of the HPA-axis among young people using longitudinal data. Moreover, it remains unclear whether genetic influences could contribute to these associations. Participants were 290 children from the Twins Early Development Study. ACEs were assessed from age 3–11 years. We calculated a cumulative risk score and also derived different ACEs clusters using factor analysis and latent class analysis. HPA-axis activity was indexed by daytime salivary cortisol at age 11. Depressive symptoms were ascertained at age 21. Genetic liability to altered cortisol levels and elevated depressive symptoms was measured using a twin-based method. We performed causal mediation analysis with mixed-effects regression models. The results showed that ACEs cumulative exposure (b = −0.20, p = 0.03), bullying (b = −0.61, p = 0.01), and emotional abuse (b = −0.84, p = 0.02) were associated with lower cortisol levels at age 11. Among participants exposed to multiple ACEs, lower cortisol was related to higher depressive symptoms at age 21 (b = −0.56, p = 0.05). Lower cortisol levels mediated around 10–20% of the total associations of ACEs cumulative exposure, bullying, and dysfunctional parenting/emotional abuse with higher depressive symptoms. Genetic factors contributed to these associations, but the mediation effects of cortisol in the associations of ACEs cumulative exposure (b = 0.16 [0.02–0.34]) and bullying (b = 0.18 [0.01–0.43]) remained when genetic confounding was accounted for. In conclusion, ACEs were linked to elevated depressive symptoms in early adulthood partly through lower cortisol levels in early adolescence, and these relationships were independent of genetic confounding.

scholarly journals The co-chaperone Fkbp5 shapes the acute stress response in the paraventricular nucleus of the hypothalamus of male mice

2021 ◽  
Author(s):  
Alexander S. Häusl ◽  
Lea M. Brix ◽  
Jakob Hartmann ◽  
Max L. Pöhlmann ◽  
Juan-Pablo Lopez ◽  
...  
Keyword(s):  
Stress Response ◽  
Hpa Axis ◽  
Paraventricular Nucleus ◽  
Acute Stress ◽  
Negative Regulator ◽  
Neuron Activity ◽  
Cell Type ◽  
Specific Expression ◽  
Acute Stress Response ◽  
Cell Type Specific

AbstractDisturbed activation or regulation of the stress response through the hypothalamic-pituitary-adrenal (HPA) axis is a fundamental component of multiple stress-related diseases, including psychiatric, metabolic, and immune disorders. The FK506 binding protein 51 (FKBP5) is a negative regulator of the glucocorticoid receptor (GR), the main driver of HPA axis regulation, and FKBP5 polymorphisms have been repeatedly linked to stress-related disorders in humans. However, the specific role of Fkbp5 in the paraventricular nucleus of the hypothalamus (PVN) in shaping HPA axis (re)activity remains to be elucidated. We here demonstrate that the deletion of Fkbp5 in Sim1+ neurons dampens the acute stress response and increases GR sensitivity. In contrast, Fkbp5 overexpression in the PVN results in a chronic HPA axis over-activation, and a PVN-specific rescue of Fkbp5 expression in full Fkbp5 KO mice normalizes the HPA axis phenotype. Single-cell RNA sequencing revealed the cell-type-specific expression pattern of Fkbp5 in the PVN and showed that Fkbp5 expression is specifically upregulated in Crh+ neurons after stress. Finally, Crh-specific Fkbp5 overexpression alters Crh neuron activity, but only partially recapitulates the PVN-specific Fkbp5 overexpression phenotype. Together, the data establish the central and cell-type-specific importance of Fkbp5 in the PVN in shaping HPA axis regulation and the acute stress response.

scholarly journals Voluntary wheel running initially increases adrenal sensitivity to adrenocorticotrophic hormone, which is attenuated with long-term training

2009 ◽  
Vol 106 (1) ◽  
pp. 66-72 ◽  
Author(s):  
Jonathan E. Campbell ◽  
Nasimeh Rakhshani ◽  
Sergiu Fediuc ◽  
Silvio Bruni ◽  
Michael C. Riddell
Keyword(s):  
Stress Response ◽  
Hpa Axis ◽  
Restraint Stress ◽  
Acute Stress ◽  
Wheel Running ◽  
Male Rats ◽  
Voluntary Wheel Running ◽  
Acute Stress Response ◽  
Voluntary Wheel

Although exercise is a common and potent activator of the hypothalamic-pituitary adrenal (HPA) axis, the effects of exercise on the acute stress response are not well understood. Here, we investigated the effects of short- (2 wk) and long-term (8 wk) voluntary wheel running on adrenal sensitivity to ACTH stimulation and the acute stress response to restraint in male rats. Diurnal glucocorticoid patterns were measured on days 7 (all groups) and 35 (8-wk groups). Rats were subjected to 20 min of restraint stress on either week 1 or on week 7 of treatment to assess HPA activation. One week later, exogenous ACTH (75 ng/kg) was administered to assess adrenal sensitivity to ACTH. Following this, adrenals were collected and analyzed for key proteins involved in corticosterone (CORT) synthesis. By the end of week 1, exercising (E) animals had twofold higher peak diurnal CORT levels compared with sedentary (S) animals ( P < 0.01). CORT values were not different between groups at week 8. In response to restraint stress at week 2, CORT values in E were approximately threefold greater than in S ( P < 0.05). No difference was found between E and S rats in the response to, or recovery from, restraint at week 8. During the ACTH challenge at week 2, E demonstrated a ∼2.5-fold increase in adrenal sensitivity compared with S, while no difference was found between E and S at week 8. The expression of steroidogenic acute regulatory protein was found to be ∼50% higher in the adrenals in E compared with S at week 2 ( P < 0.05), but no difference existed between groups at week 8. These results show that volitional wheel running initially causes hyperactivation of the HPA axis, due to enhanced adrenal sensitivity to ACTH, but that these alterations in HPA activity are completely restored by 8 wk of training.

scholarly journals Adverse childhood experiences and HPA axis function in pregnant women

2018 ◽  
Vol 102 ◽  
pp. 10-22 ◽  
Author(s):  
Jenna C. Thomas ◽  
Chantelle Magel ◽  
Lianne Tomfohr-Madsen ◽  
Sheri Madigan ◽  
Nicole Letourneau ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Hpa Axis ◽  
Adverse Childhood Experiences ◽  
Childhood Experiences ◽  
Adverse Childhood

scholarly journals Psychosocial Stress and Attitudes Toward Substance Use Among College Students: An Exploratory Study

2020 ◽  
Vol 25 (4) ◽  
pp. 338-348
Author(s):  
Dominique Kornely ◽  
Kameko Halfmann
Keyword(s):  
Substance Use ◽  
Chronic Stress ◽  
Adverse Childhood Experiences ◽  
Psychosocial Stress ◽  
Acute Stress ◽  
Negative Consequences ◽  
Childhood Experiences ◽  
Acute And Chronic Stress ◽  
Adverse Childhood ◽  
The Impact

Substance use occurs on college campuses nationwide and is among the top threats to college-student health. The present study aimed to explore the impact of stress on substance use attitudes. The independent variable was acute psychosocial stress, induced using the Trier Social Stress Test. We measured chronic stress using the Adverse Childhood Experiences questionnaire. The Alcohol Purchase Task (i.e., alcohol demand, alcohol breakpoint, alcohol expenditure) and the Cognitive Appraisal of Risky Events-Revised questionnaire (i.e., expected involvement with substances and expected benefits and consequences of using substances) were the dependent variables. We predicted that participants who completed the acute stress task would report greater attitudes toward substance use behaviors and this would be more pronounced for those with higher levels of chronic stress. Acute stress did not affect willingness to pay for alcohol, F(3, 85) = 0.55, p = .65, ηp2 = 0.02, or expected positive or negative consequences from engaging in substance use, F(3, 85) = 0.44, p = .73, ηp2 = 0.02. There was a small positive association between chronic stress, as measured by adverse childhood experiences, and expected use, ρ(89) = .22, p = .04. In exploratory analyses, we found expected positive benefits of substance use to be significantly associated with expected future involvement, whereas expected negative consequences of substance use was associated with expected future involvement. Our results imply that acute and chronic stress were not significant in predicting substance use behaviors. Rather, those who expect benefits are more likely to use substances.

scholarly journals The co-chaperone Fkbp5 shapes the acute stress response in the paraventricular nucleus of the hypothalamus

2019 ◽  
Author(s):  
Alexander S. Häusl ◽  
Jakob Hartmann ◽  
Max L. Pöhlmann ◽  
Lea M. Brix ◽  
Juan-Pablo Lopez ◽  
...  
Keyword(s):  
Stress Response ◽  
Hpa Axis ◽  
Paraventricular Nucleus ◽  
Acute Stress ◽  
Negative Regulator ◽  
Immune Disorders ◽  
Fk506 Binding Protein ◽  
Main Driver ◽  
Acute Stress Response

Disturbed activation or regulation of the stress response through the hypothalamic-pituitary-adrenal (HPA) axis is a fundamental component of multiple stress-related diseases, including psychiatric, metabolic and immune disorders. The FK506 binding protein 51 (FKBP5) is a negative regulator of the glucocorticoid receptor (GR), a main driver of HPA axis regulation, and FKBP5 polymorphisms have been repeatedly linked to stress-related disorders in humans. However, the specific role of Fkbp5 in the paraventricular nucleus of the hypothalamus (PVN) in shaping HPA axis (re)activity remains to be elucidated. Using deletion, overexpression, and rescue of Fkbp5 exclusively in the PVN, we establish the fundamental importance of Fkbp5 in the HPA axis stress response. Furthermore, we show that Fkbp5 manipulation alters GR activation and elucidate the cellular complexity in the PVN, in which Fkbp5 operates.

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