Cortisol Stress Response Research Articles

Physiological stress modulation of neural drug cue reactivity in cannabis use disorder.

Rates of daily cannabis use and cannabis use disorder (CUD) are increasing in the United States. Prominent addiction theories suggest that stress potentiation of drug cue incentive salience is a central feature of disordered versus recreational drug use, which has been corroborated using a neurophysiological index of drug cue incentive salience (i.e., the late positive potential [LPP]) in adults who regularly use cannabis. However, the mechanism through which acute stress potentiates the cannabis LPP in CUD is unclear. To address this gap, cannabis LPPs were measured before and after a stress induction in 95 adults who regularly use cannabis. Physiological (hypothalamic-pituitary-adrenal [HPA] axis, heart rate, skin conductance) and subjective stress reactivity were also measured. Based on prior work, we hypothesized that cortisol stress reactivity would predict poststress cannabis LPP enhancement in more severe CUD. The hypothesis was supported and specific to HPA-axis versus autonomic or subjective stress reactivity. Acute stress potentiation of the cannabis LPP, likely via HPA-axis activation, may be a biomarker of heavy/disordered cannabis use in adults who regularly use cannabis. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Biobehavioral and affective stress responses during nicotine withdrawal: Influence of regular cannabis co-use.

Co-use of cannabis is increasing in nicotine users and presents additional challenges in addressing nicotine dependence. This study examined the links between regular co-use of cannabis and nicotine with biobehavioral and affective changes in response to stress during nicotine withdrawal and ad libitum use. Participants (N = 79) who regularly used nicotine-only, cannabis-only, both substances, or neither substance were invited to attend two laboratory stress assessment sessions. For nicotine users, one session occurred during ad libitum nicotine use and one occurred after abstinence from nicotine. During the stress sessions, participants provided saliva samples for cortisol assay and completed measures of subjective states. Cardiovascular measures were collected during resting baseline, exposure to acute stressors, and a recovery rest period. Nicotine-only users had higher average cortisol levels in the second lab session (nicotine withdrawal) relative to the first lab session (ad libitum nicotine use). Compared to nicotine non-users, nicotine users reported less positive affect and exhibited attenuated cortisol and systolic blood pressure (BP) stress responses. Cannabis users exhibited exaggerated diastolic BP responses to stress compared to cannabis non-users, and co-users of nicotine and cannabis had higher levels of cannabis craving than cannabis-only users (p < .01). This study partially replicated earlier findings on the effects of chronic nicotine use and provided novel results regarding the influence of cannabis co-use on physiological and affective responses to stress in nicotine users during nicotine withdrawal.

Associations between cortisol stress responses and limbic volume and thickness in young adults: An exploratory study.

The investigation of the relationship between neural measures of limbic structures and hypothalamic pituitary adrenal axis responses to acute stress exposure in healthy young adults has so far focused in particular on task-based and resting state functional connectivity studies. Thus, the present study examined the association between limbic volume and thickness measures and acute cortisol responses to the psychosocial stress paradigm ScanSTRESS. Using Permutation Analysis of Linear Models controlling for sex, age and total brain volume, the associations between (sex-specific) cortisol increases and human connectome project style anatomical variables of limbic structures (i.e. volume and thickness) were investigated in 66 healthy and young (18-33 years) subjects (35 men, 31 women taking oral contraceptives). In addition, exploratory (sex-specific) bivariate correlations between cortisol increases and structural measures were conducted. The present data provide interesting new insights into the involvement of striato-limbic structures in psychosocial stress processing, suggesting that acute cortisol stress responses are also associated with mere structural measures of the human brain. Thus, our preliminary findings suggest that not only situation- and context-dependent reactions of the limbic system (i.e. blood oxygenation level-dependent reactions) are related to acute (sex-specific) cortisol stress responses but also basal and somewhat more constant structural measures. Our study hereby paves the way for further analyses in this context and highlights the relevance of the topic.

Eating After Acute Psychosocial Stress in Healthy Men and Women: Sex Differences and Endocrine Mechanisms.

Overweight and obesity have become a major health burden with a higher prevalence of obesity in women than in men. Mental stress has been discussed to play a role in this context. We investigated endocrine mechanisms underlying eating after acute psychosocial stress and potential sex differences therein. A total of 32 male and 31 female healthy participants underwent the Trier Social Stress Test before they tasted ice cream in a bogus taste test 15 minutes after stress. We repeatedly assessed the stress hormone cortisol and the satiety hormone cholecystokinin (CCK) in saliva as well as perceived hunger before and up to 1 hour after stress. Lower immediate total cortisol stress reactivity predicted higher hunger (Ps ≤ .004), but was not associated with food intake (Ps ≥ .90) or total CCK release (Ps ≥ .84). As compared to men, women ate less after stress (Ps < .001) and had consistently lower levels of hunger (Ps ≤ .024) and cortisol (Ps ≤ .008) as well as a lower immediate total cortisol stress reactivity (Ps = .002). Further, they differed in the kinetics of CCK over the total experimental procedure (Ps ≤ .011), in immediate reaction to stress (Ps ≤ .038), and after eating (Ps ≤ .072), with women's CCK levels continuously decreasing while men's CCK levels were reactive. We found evidence for lower immediate total cortisol stress reactivity relating to higher perceived hunger, with lower cortisol levels in women. Unlike in men, CCK levels in women were not reactive to acute stress and eating and decreased continuously. Our results may suggest a higher risk for stress-induced eating in women.

Prenatal serotonin reuptake inhibitor antidepressant exposure, SLC6A4 genetic variations, and cortisol activity in 6-year-old children of depressed mothers: A cohort study.

Prenatal exposure to maternal depression and serotonin reuptake inhibitor (SRI) antidepressants both affect the development of the hypothalamic-pituitary-adrenal (HPA) system, possibly via the neurotransmitter serotonin (5HT). In a community cohort, we investigated the impact of two factors that shape prenatal 5HT signaling (prenatal SRI [pSRI] exposure and child SLC6A4 genotype) on HPA activity at age 6years. Generalized estimating equation (GEE) models were used to study associations between cortisol reactivity, pSRI exposure, and child SLC6A4 genotype, controlling for maternal depression, child age, and sex (48 pSRI exposed, 74 nonexposed). Salivary cortisol levels were obtained at five time points during a laboratory stress challenge: arrival at the laboratory, following two sequential developmental assessments, and then 20 and 40min following the onset of a stress-inducing cognitive/social task. Cortisol decreased from arrival across both developmental assessments, and then increased across both time points following the stress challenge in both groups. pSRI-exposed children had lower cortisol levels across all time points. In a separate GEE model, we observed a lower cortisol stress response among children with LG /S alleles compared with children with La/La alleles, and this was particularly evident among children of mothers reporting greater third trimester depressed mood. Our findings suggest that pSRI exposure and a genetic factor associated with modulating 5HT signaling shaped HPA reactivity to a laboratory stress challenge at school age.

Unlocking the Potential of Zebrafish Research with Artificial Intelligence: Advancements in Tracking, Processing, and Visualization.

Zebrafish have become a widely accepted model organism for biomedical research due to their strong cortisol stress response, behavioral strain differences, and sensitivity to both drug treatments and predators. However, experimental zebrafish studies generate substantial data that must be analyzed through objective, accurate, and repeatable analysis methods. Recently, advancements in artificial intelligence (AI) have enabled automated tracking, image recognition, and data analysis, leading to more efficient and insightful investigations. In this review, we examine key AI applications in zebrafish research, including behavior analysis, genomics, and neuroscience. With the development of deep learning technology, AI algorithms have been used to precisely analyze and identify images of zebrafish, enabling automated testing and analysis. By applying AI algorithms in genomics research, researchers have elucidated the relationship between genes and biology, providing a better basis for the development of disease treatments and gene therapies. Additionally, the development of more effective neuroscience tools could help researchers better understand the complex neural networks in the zebrafish brain. In the future, further advancements in AI technology are expected to enable more extensive and in-depth medical research applications in zebrafish, improving our understanding of this important animal model. This review highlights the potential of AI technology in achieving the full potential of zebrafish research by enabling researchers to efficiently track, process, and visualize the outcomes of their experiments.

The influence of intensive care treatment in infancy on cortisol levels in childhood and adolescence

BackgroundInfants admitted to the intensive care unit experience numerous early-life stressors, which may have long-term effects on hypothalamic-pituitary-adrenal axis functioning. AimsTo determine the effects of intensive care treatment and related exposure to stress, pain, and opioids in infancy on cortisol levels in childhood and adolescence. Study designCross-sectional study. SubjectsChildren and adolescents aged 8 to 18 years with a history of intensive care treatment in infancy and healthy controls. The intensive care treatment cohort consisted of four subgroups with varying levels of exposure to stress, pain, and opioids in infancy. They received either mechanical ventilation, extracorporeal membrane oxygenation, major surgery, or excochleation of a giant congenital melanocytic nevus. Outcome measuresBetween-group differences in stress reactivity to a study visit consisting of pain threshold testing and an MRI examination and diurnal cortisol levels, as measured in saliva. ResultsAfter adjustment for age, sex, and gestational age, the diurnal cortisol output (AUCg) in the overall intensive care group (N = 76) was 18 % (approximately 1000 nmol/L) (95 % CI [−31 %, −3 %], P = 0.022) lower than that in the control group (N = 67). Cortisol awakening response, diurnal decline, and stress reactivity neither differed significantly between the overall intensive care group and control group, nor between the intensive care subgroups and control group. ConclusionChildren and adolescents with a history of intensive care treatment in infancy have similar cortisol profiles to those of healthy controls, except for an 18 % lower diurnal cortisol output. The clinical relevance of this reduction is yet to be determined.

Relationship of stress-reactive cortisol to suicidal intent of prior attempts in major depression

Higher intent suicide attempts carry elevated risk of future suicidal behavior. Abnormal functioning of the hypothalamic-pituitary-adrenal (HPA) axis is both linked to nonfatal suicidal behavior and suicide deaths in major depressive disorder. Few studies, however, have identified biological markers of a high-intent suicidal subgroup. We examined HPA axis output and reactivity to the Trier Social Stress Test (TSST) via salivary cortisol in depressed individuals (N=68) with a suicide attempt (SA) history. A median split of higher and lower suicidal intent scores was used to define groups. Individuals with high intent SA had attenuated total cortisol output (AUCg), F(1,60)=10.04, SE=5.095, p=.003, and lower HPA-axis stress responsivity to the TSST (AUCi), F(1,60)=4.50, SE=4.604, p=.039, compared with the low intent SA group. The high intent group also reported more pronounced negative affect than the low intent group (F[1,61]=6.413, SE=10.55, p=.014) both at baseline (meandiff=22.32, p=.038) and in response to the stressor task (meandiff=37.62, p=.003). Vulnerability to suicidal behavior in high-intent individuals may be related to the combined profile of impaired physiological responses to stress and greater negative affectivity. This clinical and biologic subgroup may benefit from targeted suicide prevention interventions.

Investigating the effect of hormonal contraceptive use on salivary cortisol response to a CO2 challenge

Hormonal contraceptive (HC) use has been associated with many physiological effects, such as blunted cortisol stress responses, when compared to naturally cycling (NC) women. However, no previous studies comparing these groups have utilized a CO2 challenge to induce stress. Therefore, the aim of the current study was to use a CO2 challenge to compare cortisol stress reactivity in women using HC relative to NC women. While this task has been previously used to induce panic, few studies have assessed its effects on cortisol, especially as it relates to HC use. Thirty-five women (19 current HC users,16 self-reported NC women) were assessed in the lab. Participants had a mean age of 25.2 years and were 74.3% White. A 35% CO2 challenge was used to provoke a stress response. Saliva samples were collected to measure cortisol (1 pre-stress baseline sample, 5 post-stress samples). Linear mixed effects modeling was used to examine whether there was a significant increase in cortisol following the challenge. There were no group differences in baseline cortisol (b = -.0117, p =.801), however, there was a significant difference in cortisol responses from baseline, with NC women having a more robust cortisol response (linear effect, b=.0065, p=.001; quadratic effect, b=-.0001, p<.001). Results are consistent with previous research demonstrating a more blunted cortisol response to a laboratory-based stressor among individuals using HC. In contrast, participants in the NC group displayed greater post-stress peak cortisol levels and a clear down-regulatory response.

Impact of Community Policing on Biological Markers of Health Across Development in Black Youth

Policing inequities are harmful sources of systemic racism perpetuated disproportionately against Black Americans. This includes unjust police encounters in Black communities such as racial profiling, stop-and-frisk, hyperpolicing, aggressive policing, police brutality, and police shootings. A knowledge gap exists in how this mistreatment, via direct or intergenerational exposure, impacts physiological systems in Black youth. Using three studies, we tested how exposure to unjust policing biologically “gets under the skin” of Black youth from infancy to emerging adulthood. Study 1 (IDS) examined associations between neighborhood stop-and-frisk rates and telomere length in infants. Study 2 (NSPAC) explored associations between mothers’ experience of unfair treatment by police and developmental and stress related hormone coupling in their children ages 5-15. Study 3 (SDRG) tested whether encounters with police in the 8th grade had a lasting impact on diurnal and waking cortisol six years later during emerging adulthood. Rates of neighborhood stop-and-frisk were associated with shorter telomeres in infants (study 1, IDS). Children whose mothers experienced unfair treatment from police showed, during the TSST, blunted cortisol stress reactivity, slower cortisol recovery, and altered cortisol-testosterone coupling (study 2, NSPAC). Adolescents who experienced police encounters had higher waking cortisol as emerging adults (study 3, SDRG). Policing inequities were linked to biological markers of stress and health across all developmental stages of Black youth. Direct, within child’s neighborhoods and intergenerational unjust policing were associated with stress-responsive biological pathways in Black youth. Findings represent a critical and modifiable target when seeking to address persistent racial inequity.

Biological Embedding of Social Determinants of Health in Early Life and Across Generations

Population health disparities represent one of the most significant public health challenges. These disparities are evident from the earliest stages of life onwards, persist across the life span, are perpetuated across generations, and are strongly influenced by social and environmental factors. Chronic stress and stress-related biobehavioral processes are discussed as one of the major effectors of the causal pathways linking upstream social determinants with health and health disparities. It is evident that the effects of stress exposure can persist over long periods of time, even across the lifespan, and particularly so if exposure occurs during sensitive developmental windows such as the intrauterine period. In this symposium, presenters will address key questions and knowledge gaps regarding biological embedding of social disadvantage and the role of stress in this context, particularly during pregnancy and early life. Tom O’Connor will present data from the ECHO-UPSIDE cohort, a longitudinal pregnancy cohort study of a socio-economically and racially/ethnically diverse sample at elevated psychosocial risk but normal medical risk status. Results indicate that maternal pre-pregnancy adversity in early childhood is associated with prenatal behavioral and physical health markers, including depressive and anxiety symptoms, stress, body mass index (BMI), sleep disturbance, and diet, as well as maternal-fetal-placental biological markers that predict child health outcomes. Laura Scholaske will present results of a multi-site prospective pregnancy study conducted in Germany that includes people of Turkish origin that are among the biggest migrant groups in Germany. Results of the study suggest that pregnant women of Turkish origin exhibit higher psychological stress levels and alterations in stress-related biological systems (i.e., elevated inflammatory levels, blunted cortisol awakening response and flatter diurnal cortisol slope) compared to non-migrant pregnant women. Shannin N. Moody will address the effects of policing inequities that are one of the most harmful sources of systemic racism perpetuated against Black Americans. In three separate studies, she tested how unjust police encounter biologically “get under the skin” in Black youth from infancy to emerging adulthood. Rates of neighborhood stop-and-frisk were associated with shorter telomeres in infants. Children whose mothers experienced unfair treatment from police showed, during the TSST, blunted cortisol stress reactivity, slower cortisol recovery, and altered cortisol-testosterone coupling. Adolescents who experienced police encounters had higher waking cortisol as emerging adults. Taken together, the studies point so some of the potential pathways through which social determinants of health may propagate and transmit persisting health disparities. Elisabeth Shirtcliff will lead a discussion on the potential implications for early prevention and targeted intervention strategies to prevent or reverse biological embedding of social disadvantage in at risk individuals.

Does a laboratory-based CO2 challenge induce a hypothalamic-pituitary-adrenal (HPA) axis stress response in healthy adults?

A methodological limitation to studying hypothalamic-pituitary-adrenal (HPA) axis functioning is that there are few laboratory-based tasks that consistently induce a stress response. Moreover, most tasks use a socially-evaluative approach to eliciting a stress response. The aim of the current study was to test whether a CO2 inhalation challenge (originally designed to induce panic symptoms) produces a robust HPA-axis stress response. Forty-eight adults (mean age = 25.6; 69% women; 73% white) were recruited from a local university in the mid-southern part of the United States. Participants were asked to complete a 35% CO2 inhalation challenge. Six saliva samples were collected to measure cortisol responses to the task (a pre-stress baseline sample followed by 5 post-stress samples). Linear mixed effects modeling was used to examine whether there was a significant increase in cortisol following the challenge. There was substantial between-subjects variability in cortisol responses to the challenge. That said, the mean group cortisol response indicated that participants experienced an increase in cortisol 15-30 minutes post-challenge and a subsequent decrease in cortisol 45-60 minutes post-challenge (linear effect, b=0.007, p<0.001; quadratic effect, b=-0.0001, p<0.001). On average, there was a 53% increase in cortisol from baseline and nearly two-thirds of participants had at least a 45% increase in cortisol. The data suggest that a CO2 inhalation challenge can be used to induce a cortisol stress response among healthy participants and offers an alternative laboratory-based task that does not rely on socially-evaluative cues to induce stress.

Neural habituation during acute stress signals a blunted endocrine response and poor resilience.

A blunted hypothalamic-pituitary-adrenal (HPA) axis response to acute stress is associated with psychiatric symptoms. Although the prefrontal cortex and limbic areas are important regulators of the HPA axis, whether the neural habituation of these regions during stress signals both blunted HPA axis responses and psychiatric symptoms remains unclear. In this study, neural habituation during acute stress and its associations with the stress cortisol response, resilience, and depression were evaluated. Seventy-seven participants (17-22 years old, 37 women) were recruited for a ScanSTRESS brain imaging study, and the activation changes between the first and last stress blocks were used as the neural habituation index. Meanwhile, participants' salivary cortisol during test was collected. Individual-level resilience and depression were measured using questionnaires. Correlation and moderation analyses were conducted to investigate the association between neural habituation and endocrine data and mental symptoms. Validated analyses were conducted using a Montreal Image Stress Test dataset in another independent sample (48 participants; 17-22 years old, 24 women). Neural habituation of the prefrontal cortex and limbic area was negatively correlated with cortisol responses in both datasets. In the ScanSTRESS paradigm, neural habituation was both positively correlated with depression and negatively correlated with resilience. Moreover, resilience moderated the relationship between neural habituation in the ventromedial prefrontal cortex and cortisol response. This study suggested that neural habituation of the prefrontal cortex and limbic area could reflect motivation dysregulation during repeated failures and negative feedback, which might further lead to maladaptive mental states.

Sustained inflammation and high cortisol reactivity following an coronary event

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Heart and lung foundation Sweden. Background Over the last decades, significant improvements have been made in medical and lifestyle managements of patients with coronary artery disease (CAD). Nonetheless, "residual inflammatory risk" for recurrent cardiovascular events is high in this patient group and remains a diagnostic and therapeutic challenge. Activation of the NLRP3 inflammasome, involving release of interleukin (IL)-1β and IL-18 followed by their downstream target IL-6, is considered a major component of the inflammatory process in atherosclerosis. One major immunomodulator is the hypothalamic–pituitary–adrenal (HPA) axis. Interestingly, there is increasing evidence that cortisol exerts proinflammatory effects through the induction of NLRP3 expression. Purpose We investigated whether sustained inflammation was associated with altered HPA stress reactivity in patients with CAD. From 4 weeks up to 6 months after a coronary event, we measured systemic inflammation, with focus on inflammasome-related cytokines, and HPA axis hormones (ACTH and cortisol) before and after acute physical stress. Method We included 81 patients (mean age 62 years, 77 % males) and 30 controls (mean age 69 years, 67 % males). Patients underwent a standardized submaximal exercise stress test at 4 weeks (visit A) and 3-6 months after the coronary event (visit B) while controls performed one test only. Free cortisol was measured in saliva before, directly and 30 min after exercise. IL-18, IL-Ra (as a surrogate for IL-1 β), IL-6, ACTH and total cortisol were measured in plasma before and 30 min after exercise. Results At visit A, plasma levels of CRP (baseline only) and IL-6 did not differ between patients and controls while IL-18 and IL-1Ra were significantly higher in patients both before and after exercise, 500 (391-632) vs 386 (295-493), p=0.002; and 179 (141-267) vs 147 (117- 182), p=0.005, respectively(table 1). At visit B, CRP decreased while IL-18 and IL-1Ra levels remained at higher levels than controls. At both visits, patients showed a heightened cortisol reactivity (i.e. significant increase directly after exercise) while this did not occur in controls (Figure 1). At visit B, the relative increase in cortisol directly after exercise was even higher than at visit A (p=0.024). At both visits, ACTH decreased significantly after exercise in patients (p&amp;lt;0.01), probably due to negative feedback, while no change in ACTH was observed in controls. Conclusion Sustained elevations in IL-18 and IL-1Ra in CAD patients following a coronary event may indicate enhanced activity of NLRP3 inflammasome. Furthermore, patients exhibited a heightened cortisol stress reactivity, a phenomenon which has been associated with atherosclerosis progression and sedentary lifestyle in the population. It may be speculated that HPA axis alteration is directly associated with NLRP3 inflammasome activation in CAD, thus opening doors to new insights in prevention. However, this remains to be further investigated.

Hair endocannabinoids predict physiological fear conditioning and salivary endocannabinoids predict subjective stress reactivity in humans

On the basis of substantial preclinical evidence, the endogenous cannabinoid system has been proposed to be closely involved in stress reactivity and extinction of fear. Existing human research supports this proposal to some extent, but existing studies have used only a narrow range of tools and biomatrices to measure endocannabinoids during stress and fear experiments. In the present study we collected hair and saliva samples from 99 healthy participants who completed a fear conditioning and intrusive memory task. Subjective, physiological and biological stress reactivity to a trauma film, which later served as unconditional stimulus during fear conditioning, was also measured. We found that salivary endocannabinoid concentrations predicted subjective responses to stress, but not cortisol stress reactivity, and replicated previous findings demonstrating a sex dimorphism in hair and salivary endocannabinoid levels. Hair 2-arachidonoyl glycerol levels were significantly associated with better retention of safety learning during extinction and renewal phases of fear conditioning, while hair concentrations of oleoylethanolamide and palmitoylethanolamide were associated with overall physiological arousal, but not conditional learning, during fear conditioning. This study is the first to test the relationship between hair and salivary endocannabinoids and these important psychological processes. Our results suggest that these measures may serve as biomarkers of dysregulation in human fear memory and stress.

The Moderating Role of Social Support on the Cortisol Stress Response of Expectant Fathers Exposed to Adverse Childhood Experiences

The Moderating Role of Social Support on the Cortisol Stress Response of Expectant Fathers Exposed to Adverse Childhood Experiences

Maximal telomerase activity capacity (mTAC) underlies the link between the cortisol response to stress and telomere length

Exposure to various forms of stress has been associated with shorter telomere length (TL). However, the molecular underpinnings of this effect are poorly understood. Based on an understanding of the key role of the reverse transcriptase enzyme telomerase in regulating TL, and building upon our previous work in developing and validating a biomarker of the capacity of cells to express telomerase (maximal telomerase activity capacity (mTAC)), we examine here the hypotheses that mTAC is positively associated with TL and that the effect of stress on TL is mediated by individual differences in mTAC. In a proof-of-principle study of 28 healthy women and men we quantified the cortisol response to a standardized stress challenge, the Trier Social Stress Test (TSST), and we concurrently assessed peripheral blood mononuclear cell (PBMC) mTAC and TL. Our results indicated that higher mTAC levels were associated with longer TL (r = 0.50, p = .01). Moreover, mediational analysis suggested that the effect of the cortisol stress response on TL was mediated by mTAC (completely standardized β = −0.17, bootstrap CI95 %: −0.44 to −0.01). Thus, our findings support the premise that individual differences in the capacity of cells to up-regulate telomerase may represent a key mediator in the link between stress and TL.

Adverse Childhood Experiences: Associations with a Blunted Cortisol Stress Response During Pregnancy.

Adverse Childhood Experiences (ACEs) are associated with a range of negative physical and mental health outcomes, yet there is limited research focused on the effect of ACEs on stress responses during pregnancy. Expectant mothers experience an increase in cortisol levels as pregnancy progresses, with this increase having important implications for fetal and early infant development. Little is known about the impact of ACEs on maternal cortisol levels. This study explored the relationship between maternal ACEs and cortisol response among expectant mothers nearing or in the third trimester of pregnancy. 39 expectant mothers were exposed to a Baby Cry Protocol via an infant simulator, with salivary cortisol collected at five points in time (N = 181). Stepwise, multilevel model creation resulted in a random intercept and random slope model with an interaction term for total number of ACEs and week of pregnancy. The repeated measures data showed that cortisol levels decreased across collection times, from arrival at the lab, through the Baby Cry Protocol, to recovery. Predictive margins for the interaction term showed that while exposure to a greater number of ACEs was associated with higher cortisol levels early in the third trimester, the expected increase in cortisol late in pregnancy was blunted for expectant mothers who were exposed to a greater number of ACEs. These findings findings suggest the importance of ACEs screening and intervention efforts as part of prenatal care.

Hair Cortisone Predicts Lower Stress-induced Salivary Cortisol Response: Resting-state Functional Connectivity Between Salience and Limbic Networks

Previous studies revealed that high long-term hypothalamic–pituitaryadrenal (HPA) axis activity measured by the hair cortisol concentrations predicts lower acute stress cortisol response and reported the influences of hair cortisol on brain activity during acute stress exposure. However, considering that long-term HPA axis activity has a close relationship with the brain’s resting-state functional connectivity (RSFC), the current study aimed to explore the role of RSFC between limbic and salience network in this relationship. Seventy-seven healthy participants underwent resting-state imaging scans before performing the acute ScanSTRESS task. Saliva samples were collected to assess the levels of acute stress salivary cortisol. Hair samples were also collected, and the corticosteroid concentration extracted from these samples were used as a biomarker of long-term HPA axis activity. High hair cortisone (HairE) levels predicted lower acute stress cortisol response. Moreover, high HairE levels were significantly correlated with enhanced RSFC between limbic and salience networks, while RSFC was negatively associated with acute stress cortisol response. Importantly, the RSFC between left insula and left parahippocampus mediated the association between HairE and acute cortisol stress response. Taken together, this study uncovers the important role of RSFC between salience and limbic networks in the long-term relationship between HairE and acute cortisol response and contributes to a deeper understanding of the individual differences in acute stress response.

Stress, hypothalamic pituitary adrenal axis activity and autonomic nervous system function in adolescents with insomnia

IntroductionAbnormal stress responses have been linked to the etiology of insomnia. We investigated the relationship between insomnia, stress, hypothalamic-pituitary-adrenal (HPA) axis activity, and autonomic nervous system (ANS) function in adolescence. MethodsForty-seven post-pubertal adolescents (16–20 years old, 28 female) with (N = 16; insomnia group) and without (N = 31; control group) DSM-5 insomnia symptoms were assessed for stress levels and stress reactivity and underwent a standardized stress protocol (Trier Social Stress Test (TSST)), after an overnight laboratory stay. Cortisol was measured upon awakening and 30-minutes later to calculate the cortisol awakening response (CAR). During the TSST, perceived stress, salivary cortisol (HPA activity), heart rate (HR) and blood pressure (BP) measures were collected. ResultsParticipants in the insomnia group reported more stress from school performance and work overload, with insomnia girls experiencing more stress from peer pressure and future uncertainty than control girls (p < 0.05). No group differences were detected in the CAR and pre-TSST stress levels. All participants showed significant increases in perceived stress (~19 %), HR (~33 %), systolic (~13 %), and diastolic (~15 %) BP in response to the TSST (p < 0.05). Overall HR stress response did not differ between groups, but was lower in boys with insomnia than in girls with insomnia (p < 0.05). Cortisol stress responses were inconclusive, possibly due to a masking effect of CAR, as the task was performed shortly after awakening and larger CARs were associated with blunted cortisol stress responses. DiscussionResults mostly show no group difference in physiological stress responses, although some interaction effects suggest a potential sex by insomnia interaction. Larger samples are needed to understand the physiological disturbances of insomnia in adolescence.