Stress Hormone System Research Articles

Opposing effects of pre-encoding stress on neural substrates of item and emotional contextual source memory retrieval

Although the mediating role of the stress hormone systems in memory for single— especially emotional— events is well-stablished, less is known about the influence of stress on memory for associated contextual information (source memory). Here, we investigated the impact of acute stress on the neural underpinnings of emotional contextual source memory. Participants underwent a stress or a control manipulation before they encoded objects paired with pleasant, neutral, or unpleasant backgrounds. One week later, item and contextual source memory were tested. Acute stress modulated the neural signature of item and contextual source memory in an opposite fashion: stressed participants showed larger activation in the precuneus and the medial prefrontal cortex (mPFC) during the retrieval of items, while the retrieval of contextual unpleasant information was associated with lower activation in the angular gyrus (AG) and mPFC. Furthermore, as revealed by cross-region representational similarity analyses, stress also reduced the memory reinstatement of the previously encoded visual cortex representations of object/unpleasant background pairings in the AG and mPFC. These results suggest that pre-encoding stress induction increases the activity of memory-related regions for single items but reduces the activity of these regions during the retrieval of contextual unpleasant information. Our findings provide new insights into the dissociative effects of stress on item and contextual source memory which could have clinical relevance for stress-related disorders.

Precision Psychiatry Approach to Treat Depression and Anxiety Targeting the Stress Hormone System - V1b-antagonists as a Case in Point.

The future of depression pharmacotherapy lies in a precision medicine approach that recognizes that depression is a disease where different causalities drive symptoms. That approach calls for a departure from current diagnostic categories, which are broad enough to allow adherence to the "one-size-fits-all" paradigm, which is complementary to the routine use of "broad-spectrum" mono-amine antidepressants. Similar to oncology, narrowing the overinclusive diagnostic window by implementing laboratory tests, which guide specifically targeted treatments, will be a major step forward in overcoming the present drug discovery crisis.A substantial subgroup of patients presents with signs and symptoms of hypothalamic-pituitary-adrenocortical (HPA) overactivity. Therefore, this stress hormone system was considered to offer worthwhile targets. Some promising results emerged, but in sum, the results achieved by targeting corticosteroid receptors were mixed.More specific are non-peptidergic drugs that block stress-responsive neuropeptides, corticotropin-releasing hormone (CRH), and arginine vasopressin (AVP) in the brain by antagonizing their cognate CRHR1-and V1b-receptors. If a patient's depressive symptomatology is driven by overactive V1b-signaling then a V1b-receptor antagonist should be first-line treatment. To identify the patient having this V1b-receptor overactivity, a neuroendocrine test, the so-called dex/CRH-test, was developed, which indicates central AVP release but is too complicated to be routinely used. Therefore, this test was transformed into a gene-based "near-patient" test that allows immediate identification if a depressed patient's symptomatology is driven by overactive V1b-receptor signaling. We believe that this precision medicine approach will be the next major innovation in the pharmacotherapy of depression.

Is your stress my stress? A standardized, randomized-controlled paradigm to study physiological stress contagion based on direct stress observation

Background & objectivesExisting research indicates that not only own stress leads to physiological stress reactions, but also observing stress in others. So far, a standardized paradigm to reliably induce physiological stress contagion based on direct face-to-face stress observation compared to an active placebo-stress observing control condition is lacking. Here, we tested a standardized randomized placebo-controlled experimental paradigm to investigate physiological reactivity to direct stress observation and characterized the stress contagion response of the major endocrine stress systems, including full reactivity kinetics. MethodsHealthy young male participants were randomly assigned to (1) undergo an adapted version of the Trier Social Stress Test (“TSST participants”, n = 20), (2) observe it (“stress observers”, n = 36), or (3) observe a corresponding placebo-stress control condition (“placebo-stress observers”, n = 30). We repeatedly assessed heart rate, salivary alpha-amylase, salivary cortisol, and salivary aldosterone. ResultsStress observers exhibited greater physiological reactivity to stress observation as compared to placebo-stress observers to placebo-stress observation in heart rate, salivary alpha-amylase, and cortisol (p’s ≤ .027), but not in aldosterone. We observed similar reactivity kinetics in TSST participants and stress observers but less pronounced in stress observers. DiscussionExtending previous literature, our findings indicate that independent of secondary effects of the observation setting, direct observation of stress in other individuals induces activation of the hypothalamus-pituitary-adrenal axis and the sympathetic-adrenal-medullary axis. Moreover, the physiological stress contagion response resembles the physiological reactivity to first-hand stress but is less pronounced. Potential implications of physiological stress contagion regarding health, cognition, or behavior, as well as modulating factors need to be further elucidated.

Impact and Role of Hypothalamic Corticotropin Releasing Hormone Neurons in Withdrawal from Chronic Alcohol Consumption in Female and Male Mice.

Worldwide, alcohol use and abuse are a leading risk of mortality, causing 5.3% of all deaths (World Health Organization, 2022). The endocrine stress system, initiated by the peripheral release of corticotropin releasing hormone (CRH) from primarily glutamatergic neurons in the paraventricular nucleus of the hypothalamus (PVN), is profoundly linked with alcohol use, abuse, and relapse (Blaine and Sinha, 2017). These PVN CRH-releasing (PVNCRH) neurons are essential for peripheral and central stress responses (Rasiah et al., 2023), but little is known about how alcohol affects these neurons. Here, we show that two-bottle choice alcohol consumption blunts the endocrine-mediated corticosterone response to stress during acute withdrawal in female mice. Conversely, using slice electrophysiology, we demonstrate that acute withdrawal engenders a hyperexcitable phenotype of PVNCRH neurons in females that is accompanied by increased glutamatergic transmission in both male and female mice. GABAergic synaptic transmission was unaffected by alcohol history. We then tested whether chemogenetic inhibition of PVNCRH neurons would restore stress response in female mice with a history of alcohol drinking in the looming disk test, which mimics an approaching predator threat. Accordingly, inhibition of PVNCRH neurons reduced active escape in hM4Di alcohol history mice only. This study indicates that stress-responsive PVNCRH neurons in females are particularly affected by a history of alcohol consumption. Interestingly, women have indicated an increase in heavy alcohol use to cope with stress (Rodriguez et al., 2020), perhaps pointing to a potential underlying mechanism in alcohol-mediated changes to PVNCRH neurons that alter stress response.SIGNIFICANCE STATEMENT Paraventricular nucleus of the hypothalamus neurons that release corticotropin releasing hormone (PVNCRH) are vital for stress response. These neurons have been understudied in relation to alcohol and withdrawal despite profound relations between stress, alcohol use disorders (AUD), and relapse. In this study, we use a variety of techniques to show that acute withdrawal from a history of alcohol impacts peripheral stress response, PVNCRH neurons, and behavior. Specifically, PVNCRH are in a hyperactive state during withdrawal, which drives an increase in active stress coping behaviors in female mice only. Understanding how alcohol use and withdrawal affects stress responding PVNCRH neurons may contribute to finding new potential targets for the treatment of alcohol use disorder.

Toxicity and effects on anuran tadpole metamorphosis of the anthranilic diamide insecticides chlorantraniliprole and cyantraniliprole

ABSTRACT The present study examined the acute and chronic toxicity attributed to commercial formulations of the anthranilic diamide insecticides chlorantraniliprole (CHLO) and cyantraniliprole (CYAN) on the neotropical amphibian species Rhinella arenarum, Rhinella fernandezae and Scinax granulatus. The median lethal concentrations obtained after 96 hr exposure (96 hr-LC50) were generally greater than 100 mg/L, except for stage 25 S. Granulatus, which were the most sensitive animals tested with a 96 hr-LC50 value of 46.78 mg/L. In subchronic exposures of R. arenarum, the 21day-LC50 were 151.4 mg/L for CHLO and >160 mg/L for CYAN, the weight gain of the tadpoles during this period not being markedly affected in both cases. Finally, when tadpoles of R. arenarum were exposed to CHLO throughout the metamorphic process, an inverted U-shaped non-monotonic dose-response relationship was observed between exposure concentrations and both % of individuals transiting between stage 39 and 42 and the time required to accomplish this. Data obtained raise the hypothesis of an effect of CHLO on the hypothalamic-pituitary-thyroid (HPT) axis, either directly or through an interaction with the stress-hormone system, as metamorphic progression from stage 39 to S42 occurs under the strict control of thyroid hormones. These observations are important as the anthranilic diamide insecticides are not currently known as endocrine disruptors. Further investigations are needed to clarify the pathways leading to these effects and examine whether environmentally-relevant aquatic concentrations of anthranilic diamides might be impacting amphibian populations in the wild.

33562 Understanding mental stress and skin aging connection among dermatologists and psychologists through real world evidence

Preaging is an emerging concept in China whereby young women are looking for skin aging solutions. Among the intrinsic and extrinsic causes of skin aging, mental stress was highlighted as a possible cause of preaging in young women. The COVID-19 pandemic has further impacted the mental well-being of the younger generation, with 44% of Asian women aged 18 to 34 under poor mental well-being based on WHO-5. While 76.5% of dermatologists agreed that there is a strong connection between stress and skin aging, there is limited evidence on the pathophysiology. The aim of this research is to explore how clinicians understand the impact of stress and the biologic pathways connecting stress and skin aging. A quantitative survey with 60 dermatologists and 60 psychologists from China and Japan was conducted to assess the link between stress and skin aging. Overall, 69.2% of both health care professionals agree that psychological stress has a significant link to skin aging. Three meta-themes were perceived by clinician as possible pathways connecting psychological stress and skin aging, including stress hormone, inflammation, and overactive immune system. While all health care professionals have heard of inflammaging, only 52% are very familiar with the concept. Both groups agree that unresolved acute inflammatory response can accelerate skin aging. Surprisingly, a significant difference was observed in that psychologists believe more strongly than dermatologists that chronic low-grade inflammation accelerates skin aging. This study highlights the need for further fundamental research, which could help clinicians provide appropriate recommendations for patients under psychological stress.

The Neurobiology of Childhood Trauma - Aldosterone and Blood Pressure Changes in a Community Sample

Childhood trauma is an important risk factor for onset and course of psychiatric disorders and particularly major depression. Recently, the renin-angiotensin-aldosterone system, one of the core stress hormone systems, has been demonstrated to be modified by childhood trauma.

The neurobiology of childhood trauma - aldosterone and blood pressure changes in a community sample

Objective: Childhood trauma is an important risk factor for onset and course of psychiatric disorders and particularly major depression. Recently, the renin-angiotensin-aldosterone system, one of the core stress hormone systems, has been demonstrated to be modified by childhood trauma. Methods: Childhood trauma was obtained using the Childhood Trauma Questionnaire (CTQ) in a community-dwelling sample (N = 2038). Plasma concentrations of renin and aldosterone were measured in subjects with childhood trauma (CT; N = 385) vs. subjects without this experience (NoCT; N = 1,653). Multivariable linear regression models were calculated to assess the associations between CTQ, systolic and diastolic blood pressure, renin and aldosterone concentrations and the ratio of aldosterone and systolic blood pressure (A/SBP). Results: CT subjects demonstrated higher plasma aldosterone (A) concentrations, a lower systolic and diastolic blood pressure and a higher A/SBP. In addition, both aldosterone concentrations as well as A/SBP correlated with the severity of childhood trauma. These findings could not be attributed to differences in concomitant medication. Conclusions: In conclusion, childhood trauma was associated with neurobiological markers, which may impact the risk for psychiatric disorders, primarily major depression. The altered A/SBP ratio points to a desensitization of peripheral mineralocorticoid receptor function, which may be a target for therapeutic interventions.

Longitudinal CSF proteome profiling in mice to uncover the acute and sustained mechanisms of action of rapid acting antidepressant (2R,6R)-hydroxynorketamine (HNK)

Delayed onset of antidepressant action is a shortcoming in depression treatment. Ketamine and its metabolite (2R,6R)-hydroxynorketamine (HNK) have emerged as promising rapid-acting antidepressants. However, their mechanism of action remains unknown. In this study, we first described the anxious and depression-prone inbred mouse strain, DBA/2J, as an animal model to assess the antidepressant-like effects of ketamine and HNK in vivo. To decode the molecular mechanisms mediating HNK's rapid antidepressant effects, a longitudinal cerebrospinal fluid (CSF) proteome profiling of its acute and sustained effects was conducted using an unbiased, hypothesis-free mass spectrometry-based proteomics approach. A total of 387 proteins were identified, with a major implication of significantly differentially expressed proteins in the glucocorticoid receptor (GR) signaling pathway, providing evidence for a link between HNK and regulation of the stress hormone system. Mechanistically, we identified HNK to repress GR-mediated transcription and reduce hormonal sensitivity of GR in vitro. In addition, mammalian target of rapamycin (mTOR) and brain-derived neurotrophic factor (BDNF) were predicted to be important upstream regulators of HNK treatment. Our results contribute to precise understanding of the temporal dynamics and molecular targets underlying HNK's rapid antidepressant-like effects, which can be used as a benchmark for improved treatment strategies for depression in future.

Low Corticosterone Response to Stress in a Perimenopausal Rat Model Is Associated with the Hypoactivation of PaMP Region of the Paraventricular Nucleus and Can Be Corrected by Exogenous Progesterone Supplementation

Introduction: The transition to menopause is characterized by mood, behavioral and metabolic changes. However, little is known about the changes in adrenal response to stress. Aims: The aim of the study was to evaluate, in an animal model of perimenopause induced by 4-vinylcyclohexene diepoxide (VCD), (1) the endocrine and neuronal stress system activity in response to acute restraint stress and (2) the effect of hormonal therapy in this response. Methods: Prepubertal female Wistar rats received daily injections (s.c) of oil or VCD (160 mg/kg) for 15 days. On 56th–66th days after treatment onset, the groups to be stressed received s.c implants containing placebo (PL), 17β-estradiol (E2), progesterone (P4), or E2P4. At 80 ± 5 days after VCD/oil injections, stress was applied for 30 min. Blood samples were collected immediately after and 60 min after the end of stress session from the tail tip followed by transcardial perfusion with PFA 4% for the assessment of c-Fos expression in the medial and posterior parvocellular (PaMP and PaPo) subdivisions of the paraventricular nucleus (PVN) and c-Fos/tyrosine hydroxylase in the locus coeruleus (LC) using immunohistochemistry. Control groups were not stressed nor received hormone therapy. Results: While basal corticosterone levels were similar between VCD-periestropausal and control rats, the secretion in response to stress in the VCD group was lower. This effect was prevented by P4 therapy. Inversely, basal levels of P4 were lower in VCD-periestropausal rats than in the controls, and no differences were found in response to stress between the groups. As expected, 30-min restraint stress increased c-Fos immunoreactivity in all brain areas studied in both control and VCD-periestropausal rats. However, the c-Fos increase in the PaMP region was attenuated. In all areas examined, there were no significant differences in the number of c-Fos-positive neurons across hormonal therapies. Discussion/Conclusion: This is the first study to demonstrate in a perimenopausal rat model that reproductive aging is accompanied by inadequate secretion of corticosterone in response to acute stress in association with the hypoactivation of the PaMP region of the PVN, while adrenal P4 response is preserved. Moreover, P4 therapy was shown to attenuate the effects of progressive ovarian failure on adrenal functioning during stress.

Sex-specific associations of basal steroid hormones and neuropeptides with Conduct Disorder and neuroendocrine mediation of environmental risk

Conduct Disorder (CD) is characterized by severe aggressive and antisocial behavior. The stress hormone system has frequently been investigated as a neurobiological correlate of CD, while other interacting neuroendocrine biomarkers of sex hormone or neuropeptide systems have rarely been studied, especially in females. We examined multiple basal neuroendocrine biomarkers in female and male adolescents with CD compared to healthy controls (HCs), and explored whether they mediate effects of environmental risk factors on CD. Within the FemNAT-CD study, salivary cortisol, alpha-amylase, testosterone, dehydroepiandrosterone-sulfate (DHEA-S), estradiol, progesterone, oxytocin, and arginine-vasopressin were measured under basal conditions in 166 pubertal adolescents with CD, and 194 sex-, age-, and puberty-matched HCs (60% females, 9–18 years). Further, environmental risk factors were assessed. Single hormone analyses showed higher DHEA-S, and lower estradiol and progesterone levels in both females and males with CD relative to HCs. When accounting for interactions between neuroendocrine systems, a male-specific sex hormone factor (testosterone/DHEA-S) predicted male CD, while estradiol and a stress-system factor (cortisol/alpha-amylase) interacting with oxytocin predicted female CD. Estradiol, progesterone, and oxytocin partly explained associations between early environmental risk and CD. Findings provide evidence for sex-specific associations between basal neuroendocrine measures and CD. Especially altered sex hormones (androgen increases in males, estrogen reductions in females) robustly related to CD, while basal stress-system measures did not. Early environmental risk factors for CD may act partly through their effects on the neuroendocrine system, especially in females. Limitations (e.g., basal neuroendocrine assessment, different sample sizes per sex, pubertal participants, exploratory mediation analyses) are discussed.

Pharmacogenetic/Pharmacogenomic Tests for Treatment Prediction in Depression.

Genetic factors play a significant but complex role in antidepressant (AD) response and tolerability. During recent years, there is growing enthusiasm in the promise of pharmacogenetic/pharmacogenomic (PGx) tools for optimizing and personalizing treatment outcomes for patients with major depressive disorder (MDD). The influence of pharmacokinetic and pharmacodynamic genes on response and tolerability has been investigated, including those encoding the cytochrome P450 superfamily, P-glycoprotein, monoaminergic transporters and receptors, intracellular signal transduction pathways, and the stress hormone system. Genome-wide association studies are also identifying new genetic variants associated with AD response phenotypes, which, combined with methods such as polygenic risk scores (PRS), is opening up new avenues for novel personalized treatment approaches for MDD. This chapter describes the basic concepts in PGx of AD response, reviews the major pharmacokinetic and pharmacodynamic genes involved in AD outcome, discusses PRS as a promising approach for predicting AD efficacy and tolerability, and addresses key challenges to the development and application of PGx tests.

The Role of Endocrine Stress Systems and Sex Hormones in the Enhancing Effects of Stress on Mental Rotation Capabilities

The possible effects of stress and neurobiological stress mechanisms on visuospatial abilities remain largely unknown. In the current study, we examined the combined effect of sex hormones and both the hypothalamic–pituitary–adrenal axis (HPA-A) and the sympathetic nervous system (SNS) on stress-induced changes in visuospatial performance. A total of 107 participants completed a mental rotation task and were subsequently exposed to either to the Trier social stress test (TSST) or to a control condition before completing the mental rotation task again. HPA-A and SNS reactivity of the participants were evaluated by measuring salivary alpha amylase (sAA; an SNS activation marker) and cortisol in four saliva samples. Pre-stress levels of sex hormones (progesterone, estradiol, and testosterone) were also measured. The TSST enhanced mental rotation performance, and this enhancement was negatively correlated with baseline estradiol levels and positively correlated with the level of cortisol reactivity among men. In addition, controlling for baseline levels of testosterone, estradiol, and progesterone diminished this effect of stress. These results imply that the stress-induced facilitation of mental rotation performance is modulated by baseline sex hormones and provide preliminary support to the notion that a complex interaction between sex hormones and neuroendocrine stress mechanisms mediates the influence of stress on visuospatial performance.

Interactive role of endocrine stress systems and reproductive hormones in the effects of stress on declarative memory

The effects of stress on memory performance, and the neuroendocrine mechanisms mediating such effects, are not well understood. Given the interrelationship between reproductive hormones and both the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal axis (HPA-A), we examined their combined effect on stress-induced modulation of declarative memory. Before and after exposure either to the Trier Social Stress Test (TSST) procedure or to a non-stress condition, 112 participants completed the Rey Auditory Verbal Learning Test. We analyzed participants’ HPA-A and SNS reactivity by measuring cortisol and salivary alpha-amylase (sAA, an SNS activation marker) in four saliva samples. In addition, testosterone, estradiol, and progesterone were sampled prior to the stress exposure. Exposure to the TSST attenuated memory recall after an introduction of an interference list during the declarative memory task. Importantly, controlling for testosterone, estradiol, and progesterone diminished this effect of stress, suggesting the importance of baseline reproductive hormones in stress-induced modulation of memory functions. Furthermore, a multiple regression model revealed that stress-induced declines in memory performance were negatively associated with participants’ stress-induced cortisol reactivity, but only among individuals with high testosterone levels. In addition, stress-induced declines in memory performance were negatively associated with participants’ stress-induced increases in sAA, but only in individuals with low progesterone levels. These findings suggest that the effects of stress on memory performance may be modulated by baseline reproductive hormones and provide a preliminary indication for specific modulatory interrelationships between reproductive hormones and neuroendocrine stress mechanisms in mediating the effects of stress on memory.

Maternal early life maltreatment and psychopathology affect the next generation: Alterations in post-awakening cortisol levels of primary school-aged children.

Early life maltreatment (ELM) has severe and lasting effects on the individual, which might also impact the next generation. On an endocrine level, the hypothalamus-pituitary-adrenal axis has been suggested to play an important role in the interplay between ELM and the development of mental disorders. Several studies have revealed that maternal post-awakening cortisol concentration, maternal sensitivity, maternal ELM and psychopathology are associated with children's cortisol levels. We investigated the post-awakening cortisol concentrations in 6- to 11-year-old children (N=53) whose mothers either had experienced ELM and had developed a lifetime mental disorder (N=15 ELM and disorder group), had experienced ELM without developing a mental disorder (N=12 ELM-only group), or had neither experienced ELM nor developed a mental disorder (N=26 HC-group). Furthermore, we assessed maternal post-awakening cortisol concentrations, maternal psychopathology, and sensitivity. Multilevel analysis revealed higher cortisol at awakening (S1) levels in children of mothers with ELM and disorder. Maternal cortisol at awakening (S1) also predicted the child's cortisol at awakening (S1), and no effect of maternal sensitivity could be found. The current results replicate an attunement of cortisol levels (S1) between mothers and children and suggest an association between the children's endocrine stress system and maternal factors such as ELM and psychopathology.

Neuroendocrine Stress System in Bipolar Disorder.

Hormones have a crucial part in the progress and manifestation of a wide variety of different behaviors. The main influence of the neuroendocrine system on behavior is its action on the neurobiology of neuropsychiatric disorders and its relationship with the pharmacodynamics of medicines. Of all the neuroendocrine axes, the hypothalamic-pituitary-adrenal (HPA) axis has been the most extensively studied. There is evidence that disturbance in the HPA axis, the primary stress hormone system, could increase treatment resistance and relapse, worsen illness outcome, and cause cognitive deficits. Glucocorticoids mediate their actions in negative feedback binding in two different cytoplasmatic receptors described as mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs). Different psychopathologies underlying bipolar disorders are supposed to involve persistent dysfunctions in the expression and role of both MR and GR in the hippocampus. We review and analyze the evidence related to the correlation between bipolar disorders and the consequences and impact of stressful life events on the HPA axis, exploring the importance of these findings in bipolar disorders and as potential new targets for treatment.

Computational Analysis of Therapeutic Neuroadaptation to Chronic Antidepressant in a Model of the Monoaminergic Neurotransmitter and Stress Hormone Systems.

The clinical practice of selective serotonin reuptake inhibitor (SSRI) augmentation relies heavily on trial-and-error. Unfortunately, the drug combinations prescribed today fail to provide relief for many depressed patients. In order to identify potentially more effective treatments, we developed a computational model of the monoaminergic neurotransmitter and stress-steroid systems that neuroadapts to chronic administration of combinations of antidepressant drugs and hormones by adjusting the strengths of its transmitter-system components (TSCs). We used the model to screen 60 chronically administered drug/hormone pairs and triples, and identified as potentially therapeutic those combinations that raised the monoamines (serotonin, norepinephrine, and dopamine) but lowered cortisol following neuroadaptation in the model. We also evaluated the contributions of individual and pairs of TSCs to therapeutic neuroadaptation with chronic SSRI using sensitivity, correlation, and linear temporal-logic analyses. All three approaches revealed that therapeutic neuroadaptation to chronic SSRI is an overdetermined process that depends on multiple TSCs, providing a potential explanation for the clinical finding that no single antidepressant regimen alleviates depressive symptoms in all patients.

Neurobiology of Self-Regulation: Longitudinal Influence of FKBP5 and Intimate Partner Violence on Emotional and Cognitive Development in Childhood.

Self-regulation includes the volitional and nonvolitional regulation of emotional, cognitive, and physiological responses to stimulation. It develops from infancy through individual characteristics and the environment, with the stress hormone system as a central player. Accordingly, the authors hypothesized that genes involved in regulating the stress system, such as FK506 binding protein 5 (FKBP5), interact with early-life stress exposure, such as exposure to intimate partner violence (IPV), to predict self-regulation indicators and associated outcomes, including behavioral and learning problems in school. Study participants were a longitudinal birth cohort of 910 children for whom FKBP5 genotypes were available and who were assessed for exposure to IPV during the first 2 years of life as well as multiple measures of self-regulation: stress-induced cortisol reactivity and fear-elicited emotional reactivity at 7, 15, and 24 months, executive function at 36, 48, and 60 months, and emotional and behavioral difficulties and reading and math achievement in school grades 1, 2, and 5. Data were analyzed using longitudinal clustering and ordinal logistic regression procedures followed by mixed linear modeling. Children with two copies of a risk FKBP5 haplotype and IPV exposure were significantly more likely to have a developmental trajectory characterized by high, prolonged stress-induced cortisol reactivity and emotional reactivity in toddlerhood, followed by low executive function at school entry and high emotional and behavior problems and low reading ability in the primary school grades. The interaction of FKBP5 and IPV affects the physiological response to stress early in life, with consequences for emotional and cognitive self-regulation. Targeting self-regulation may present an early intervention strategy for children facing genetic and environmental risk.

Abstract B162: Developmental programming of long-term immunity of CD8 T-cells by perinatal glucocorticoids

Abstract Stress has been associated with various types of diseases including cancer. It was suggested that compromised antitumor immunity is often responsible for tumor progression during stress, which is caused by immunosuppressive glucocorticoids (GC), stress hormone, and sympathetic nervous system activation. Perinatal period is critical for immunity as the first major contact with the environment is made and this interaction can shape the immune system development. Epidemiologic studies found that early-life exposure to specific environment may have life-long impact on immunity, affecting the development of immune-related diseases such as inflammatory diseases, metabolic diseases, allergic diseases as well as cancer. Nevertheless, it is still largely unknown whether developmental programming of immunity exists due to the lack of mechanistic understanding on this subject. Since most of the environmental factors that are reported to cause later-life development of diseases are associated with stress, we adopted a model to directly test the effect of stress hormone. We introduced the in vivo mouse model of perinatal glucocorticoid receptor (GR) activation via dexamethasone (DEX) treatment in drinking water perinatally (embryonic day 7.5-postnatal day 1). Then, we analyzed the T-cell immunity and tumor susceptibility when the offspring became mature. We found that perinatal exposure of DEX permanently repressed the CD8 T-cell response. Consistently, accelerated tumor growth and decreased intra-tumor CD8 T-cell response were observed with perinatal DEX exposure in B16-F10 melanoma model. In OT-I T-cell receptor transgenic model, OT-I CD8 T-cells, from the mice with perinatal DEX exposure, showed suppressed ovalbumin (OVA) antigen-specific immune response as well as repressed antitumor immune response against OVA expressing E.G7 lymphoma. Furthermore, we found CD8 T-cell population expressing glucocorticoid-induced TNF receptor-related protein (GITR) was decreased with perinatal DEX exposure. Finally, we observed that endogenous corticosterone level as well as GR signaling pathway in T-cell was reduced with perinatal DEX exposure. We also identified that GR in T-cell was required for adequate CD8 T-cell activation and survival, suggesting that reduction of endogenous GC level with perinatal DEX was responsible for suppressed CD8 T-cell function. These results showed that perinatal GC exposure persistently programed the threshold for hypothalamus-pituitary-adrenal axis for regulating endogenous GC level, and that reduced systemic GC level elicited repressed CD8 T-cell activation and survival, leading to tumor susceptibility. Citation Format: Jun Young Hong, Bharat Vaidyanathan, Jen Young Cho, Ruslan Medzhitov. Developmental programming of long-term immunity of CD8 T-cells by perinatal glucocorticoids [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B162.

수면박탈 후 해양심층수 타라소테라피 적용에 따른 스트레스 호르몬 및 자율신경계의 변화

수면박탈 후 해양심층수 타라소테라피 적용에 따른 스트레스 호르몬 및 자율신경계의 변화