Luke Hanlin

Self-compassion as a predictor of interleukin-6 response to acute psychosocial stress

We examined the hypothesis that self-compassion is associated with lower levels of stress-induced inflammation. On two consecutive days, plasma concentrations of interleukin-6 (IL-6) were assessed at baseline and at 30 and 120 min following exposure to a standardized laboratory stressor in a sample of 41 healthy young adults. Participants who were higher in self-compassion exhibited significantly lower day 1 IL-6 responses, even when controlling for self-esteem, depressive symptoms, demographic factors, and distress. Self-compassion was not related to day 2 IL-6 response but was inversely related to day 2 baseline IL-6 levels, and to increase in baseline IL-6 from day 1 to day 2. These findings suggest that self-compassion may serve as a protective factor against stress-induced inflammation and inflammation-related disease.

Measures of Adiposity Predict Interleukin-6 Responses to Repeated Psychosocial Stress

OBJECTIVE Overweight and obese individuals, who comprise approximately two-thirds of the U.S. population, are at increased risk for developing a range of diseases. This increased risk may be due in part to maladaptive stress responses within this group, including heightened low-grade inflammation and HPA axis non-habituation. In this study we tested the relationship between adiposity, plasma interleukin-6 (IL-6) and HPA axis responses to repeated stress. METHODS Sixty-seven healthy participants were exposed to the Trier Social Stress Test (TSST) on two consecutive days. We collected saliva for cortisol measurements at baseline and at 1, 10, 30, 60 and 120min post-TSST, and blood for plasma IL-6 measurements at baseline and 30 and 120min post-TSST. RESULTS Stress exposure induced significant increases of cortisol and IL-6 on both days (cortisol: F=38, p<0.001; IL-6: F=90.8; p<0.001), and repeated exposure was related with cortisol habituation (F=8.2; p<0.001) and IL-6 sensitization (F=5.2; p=0.022). BMI and body fat were related with higher cortisol responses to repeated stress (BMI: beta=0.34; p=0.014; body fat: beta=0.29; p=0.045), and with higher IL-6 responses to repeated stress (BMI: beta=0.27, p=0.044; body fat: beta=0.37; p=0.006). CONCLUSIONS Taken together, individuals with higher measures of adiposity showed less efficient HPA axis habituation as well as sensitization of IL-6 responses to repeated acute stress. These findings point to maladaptive stress response patterns in overweight humans, which, through exposure to higher levels of inflammatory mediators, might partially explain diseases related with overweight and/or obesity.

Self-compassionate young adults show lower salivary alpha-amylase responses to repeated psychosocial stress.

In this study, we tested the hypothesis that participants higher in dispositional self-compassion would show lower stress-induced reactivity of salivary alpha-amylase (sAA), a marker of sympathetic nervous system activation. Thirty-three healthy participants (18–34 years old) were exposed to a standardized laboratory stressor on two consecutive days. Self-compassion, self-esteem, and demographic factors were assessed by questionnaire, and sAA was assessed at baseline and at 1, 10, 30, and 60 min following each stressor. Self-compassion was a significant negative predictor of sAA responses on both days. This relationship remained significant when controlling for self-esteem, subjective distress, age, gender, ethnicity, and body mass index. These results suggest that self-compassion may serve as a protective factor against stress-induced physiological changes that have implications for health.

Post-stress rumination predicts HPA axis responses to repeated acute stress

Failure of the hypothalamus-pituitary-adrenal (HPA) axis to habituate to repeated stress exposure is related with adverse health outcomes, but our knowledge of predictors of non-habituation is limited. Rumination, defined as repetitive and unwanted past-centered negative thinking, is related with exaggerated HPA axis stress responses and poor health outcomes. The aim of this study was to test whether post-stress rumination was related with non-habituation of cortisol to repeated stress exposure. Twenty-seven participants (n=13 females) were exposed to the Trier Social Stress Test (TSST) twice on consecutive afternoons. Post-stress rumination was measured after the first TSST, and HPA axis responses were assessed by measuring salivary cortisol 1 min before, and 1, 10, 20, 60, and 120 min after both TSSTs. Stress exposure induced HPA axis activation on both days, and this activation showed habituation indicated by lower responses to the second TSST (F=3.7, p=0.015). Post-stress rumination after the first TSST was associated with greater cortisol reactivity after the initial stress test (r=0.45, p<0.05) and with increased cortisol responses to the second TSST (r=0.51, p<0.01), indicating non-habituation, independently of age, sex, depressive symptoms, perceived life stress, and trait rumination. In summary, results showed that rumination after stress predicted non-habituation of HPA axis responses. This finding implicates rumination as one possible mechanism mediating maladaptive stress response patterns, and it might also offer a pathway through which rumination might lead to negative health outcomes.

Response and habituation of pro- and anti-inflammatory gene expression to repeated acute stress

INTRODUCTION Acute stress induces increases in plasma inflammatory mediators, which do not habituate to repeated stress. Inflammation is a risk factor for age-related illnesses, highlighting the need to understand factors controlling inflammation. No studies have examined changes in pro- and anti-inflammatory gene expression in response to repeated acute stress in humans. METHODS RNA was isolated from peripheral blood before, 30 and 120min after exposure of n=32 healthy human participants to the Trier Social Stress Test (TSST) on two days. Gene expression of interleukin (IL)-6, IL-1β, nuclear factor (NF)-κB and IκB was measured repeatedly on both days. We further assessed leukocyte numbers, plasma IL-6, and salivary cortisol. RESULTS Stress induced IL-6 (F=44.7; p<0.001) and cortisol responses (F=18.6; p<0.001). Cortisol responses habituated (F=5.1, p=0.003), but IL-6 responses did not (n.s.). All genes increased in response to initial stress (IL-6: F=3.8; p=0.029; IL-1β: F=7.1; p=0.008; NF-κB: F=5.1; p=0.009; IκB: F=4.7; p=0.013) and showed habituation to repeated stress (IL-6: t=2.3; p=0.03; IL-1β: t=3.9; p=0.001; NF-κB: t=2.1; p=0.041; IκB: t=3.1; p=0.005). Day 1 responses of IL-1β and IκB were not explained by changes in leukocyte populations, but IL-6 and NF-κB, as well as most day 2 changes were not independent of leukocyte populations. CONCLUSIONS Stress response and habituation of pro- and anti-inflammatory gene expression as found here might indicate that even on an intracellular level, inflammatory responses to acute stress are adaptive in that they respond to initial, but habituate to repeated, similar stress. Future studies will need to test whether non-habituation is predictive of disease.

Increased alpha‐amylase response to an acute psychosocial stress challenge in healthy adults with childhood adversity

Childhood adversity is highly prevalent and linked to lasting psychological and physiological consequences. A potential mechanism for negative health outcomes is altered stress reactivity. While previous research has addressed associations of childhood adversity with stress system reactivity, sympathetic nervous system (SNS) stress reactivity is understudied. We therefore set out here to examining salivary alpha-amylase (sAA) reactivity in relation with childhood adversity. Forty-one healthy adult subjects (n = 24 male; n = 17 female) aged 18-34 years underwent the Trier Social Stress Test (TSST) and completed the Childhood Trauma Questionnaire (CTQ). Saliva for measurement of sAA was collected at three time points; before the TSST, immediately after, and 10 min post-TSST. We found that those with childhood trauma had a higher overall sAA response to the TSST, as seen in a repeated measures ANOVA (CTQ by time interaction: F(1.8,71.5) = 6.46, p = .01) and an independent samples t-test indicating higher sAA baseline to peak response (t = 3.22, p = .003). There was also a positive correlation between sAA reactivity and the CTQ subscales of childhood physical abuse (r = .46, p = .005) and emotional abuse (r = .37, p = .024). Healthy adults with low-to-moderate childhood adversity had a heightened sAA response immediately following the stressor. Higher SNS reactivity could be a link to negative health outcomes in adults with early adversity. Future research should address whether altered sAA reactivity is predictive of negative health outcomes in those with childhood adversity.

Stronger hypothalamus-pituitary-adrenal axis habituation predicts lesser sensitization of inflammatory response to repeated acute stress exposures in healthy young adults.

Effective adjustment of the stress systems to repeated stress is regarded as an adaptive response of the organism facing environmental threats. Given the intertwined relationship between the stress systems and the inflammatory system, it could be expected that inflammatory processes should adapt to repeated stress as well. However, only little is known about adaptational processes of the different components of the immune system in response to repeated stress, and how these might be related to adaptational processes of the hypothalamus-pituitary-adrenal (HPA) axis. We here examined N=22 healthy participants (mean age 23years, 50% female) and exposed them to a standardized laboratory stressor twice, 24h apart. Plasma interleukin 6 (IL-6), salivary cortisol and psychometric parameters were assessed repeatedly up to 120min post stress. Results revealed a significant day by time interaction for cortisol (F=5.06; p=0.013) and IL-6 (F=4.42; p=0.041), indicating habituation of HPA axis and sensitization of inflammatory stress responses. Cortisol habituation and inflammatory sensitization were inversely related when controlling for sex (r=-0.44; p=0.044). Explorative analyses revealed significant associations between the IL-6 response on the second exposure with perceived stress (r=0.58; p=0.004), vital exhaustion (r=0.57; p=0.009), depression (r=0.47; p=0.026) and purpose in life (r=-0.50; p=0.04). These findings may help to increase understanding of the still only rudimentary understood interplay of adaptational processes of endocrine and immune responses to repeated stress and might indicate a link between inflammatory disinhibition and psychological indicators of well-being.

HPA-axis and inflammatory reactivity to acute stress is related with basal HPA-axis activity

INTRODUCTION Inflammation is drawing attention as pathway between psychosocial stress and health, and basal HPA axis activity has been suggested to exert a consistent regulatory influence on peripheral inflammation. Here we studied the relationship between basal HPA axis activity and inflammatory and HPA axis acute stress reactivity. METHODS We recruited 48 healthy individuals and collected saliva for diurnal cortisol sampling at 6 points. Participants were previously exposed to the Trier Social Stress Test (TSST) on two consecutive days. Plasma interleukin-6 (IL-6) and salivary cortisol reactivity to acute stress were measured, and their relationships with basal HPA axis activity were analyzed. RESULTS Steeper cortisol awakening response (CAR) linear increase was related with stronger cortisol stress reactivity (γ=0.015; p=0.042) and marginally significantly with greater habituation (γ=0.01; p=0.066). Greater curvilinearity of CAR was related with stronger cortisol reactivity (γ=-0.014; p=0.021) and greater cortisol habituation (γ=-0.011; p=0.006). Steeper daily linear decline was related with significant or marginally significantly stronger cortisol and IL-6 reactivity (cortisol: γ=-0.0004; p=0.06; IL-6: γ=-0.028; p=0.031) and greater habituation (cortisol: γ=-0.002; p=0.009, IL-6: γ=-0.015; p=0.033). Greater curvilinearity of daily decline was related with stronger IL-6 reactivity (γ=0.002; p=0.024) and also greater cortisol and IL-6 habituation (cortisol: γ=0.00009; p=0.03, IL-6: γ=0.001; p=0.024). CONCLUSIONS Patterns of basal HPA axis activity that are related with healthier outcomes were found to be related with stronger initial cortisol and IL-6 reactivity and greater habituation. This is an important step in understanding the long-term health implications of acute stress responsiveness, and future studies should employ longitudinal designs to identify the direction of these relationships.

Blunted Diurnal Cortisol Activity in Healthy Adults with Childhood Adversity

Childhood adversity, such as neglect, or physical, emotional, or sexual abuse, is prevalent in the U.S. and worldwide, and connected to an elevated incidence of disease in adulthood. A pathway in this relationship might be altered hypothalamic-pituitary-adrenal (HPA) axis functioning, as a result of differential hippocampal development in early life. A blunted diurnal cortisol slope is a precursor for many disorders. While studies have focused on HPA reactivity in relation to childhood adversity, there has been markedly less research on basal HPA functioning in those with low-to-moderate adversity. Based on previous research, we hypothesized that adults with low-to-moderate childhood adversity would have altered HPA axis functioning, as evidenced by a blunted diurnal cortisol slope and altered cortisol awakening response (CAR). Healthy adults aged 18–65 (n = 61 adults; 31 males and 30 females) completed the Childhood Trauma Questionnaire. Participants provided at-home saliva samples on two consecutive days at wake-up, and 30 min, 1, 4, 9, and 13 h later; samples were averaged over the 2 days. We found that low-to-moderate childhood adversity predicted lower morning cortisol (β = -0.34, p = 0.007, R2 = 0.21), as well as a blunted cortisol slope (β = 2.97, p = 0.004, R2 = 0.22), but found no association with CAR (β = 0.19, p = 0.14, R2 = 0.12). Overall, we found that in healthy participants, low-to-moderate adversity in childhood is associated with altered basal HPA activity in adulthood. Our findings indicate that even low levels of childhood adversity may predispose individuals to disease associated with HPA dysregulation in later life.

Dietary dopamine depletion blunts reward network sensitivity to face trustworthiness

Research demonstrating responsiveness of the neural reward network to face trustworthiness has not assessed whether the effects are mediated by dopaminergic function. We filled this gap in the literature by investigating whether dietary dopamine depletion would blunt the sensitivity of neural activation to faces varying in trustworthiness across reward regions as well as the sensitivity of behavioral responses to those faces. As prolactin release is negatively regulated by dopamine, peripheral prolactin levels confirmed the efficacy of our manipulation. The dopamine depletion manipulation moderated neural activation to face trustworthiness in the amygdala, medial orbital frontal cortex, and ventral medial prefrontal cortex. Control participants (n=20) showed nonlinear and linear neural activation to face trustworthiness in the amygdala and ventral medial prefrontal cortex, and nonlinear activation in the medial orbital frontal cortex, while depleted participants (n=20) showed only a linear effect in the amygdala. Controls also showed stronger amygdala activation to high trustworthy faces than depleted participants. In contrast to effects on neural activation, dopamine depletion did not blunt the sensitivity of behavioral ratings. While this is the first study to demonstrate that dopamine depletion blunts the sensitivity of the neural reward system to social stimuli, namely faces varying in trustworthiness, future research should investigate behavioral measures that may be more responsive to dopaminergic effects than face ratings. Such research would shed further light on the possibility that individual differences in dopaminergic function that were simulated by our manipulation influence social interactions with people who vary in facial trustworthiness.