HPA Axis Regulation Research Articles

Hair cortisol and dehydroepiandrosterone and their associations with optimism and pessimism in older people

The cumulative negative effects of prolonged Hypothalamic-Pituitary-Adrenal axis (HPA axis) activation are associated with several age-related diseases. Some psychological traits such as optimism and pessimism have been shown to be related to both health and the stress response, although their relationship with the HPA axis is inconclusive. More stable HPA axis biomarkers, such as hair samples of cortisol (HC) and dehydroepiandrosterone (HDHEA), would help to clarify the association between these psychological traits and HPA axis functioning. The main aim of this study was to test the relationships between optimism and pessimism and chronic stress biomarkers measured in hair (HC and HDHEA). Additionally, a secondary objective was to explore sex differences in HC and HDHEA levels and their relationship with these psychological traits. We measured optimism, pessimism, and their combination (dispositional optimism) using the Life Orientation Test Revised (LOT-R) and chronic stress biomarkers (HC and HDHEA) in 119 healthy participants (46 men and 73 women) between 56 and 81 years old who belonged to a university program. Regression analyses controlling for perceived stress and BMI indicated that higher dispositional optimism was related to lower HC and HC:HDHEAratio (β = −0.256, p = .008 and β = −0.300, p = .002, respectively). More specifically, higher pessimism was related to higher HC (β = 0.235; p = .012) and HC:HDHEAratio (β = 0.240; p = .011), whereas higher optimism was associated with a lower HC:HDHEAratio(β = −0.205; p = .031). Moderation analyses showed no sex differences. To date, this is the first study to investigate the link between these traits and HC and HDHEA in older people. Our results confirm that positive and negative expectations about the future (i.e. optimism and pessimism) may play an important role in health due to their relationship with the HPA axis. They also strengthen the idea that the negative effects of pessimism have a greater weight than the protective effects of optimism in their relationship with HPA axis regulation.

Comprehensive assessment of cortisol and cortisol metabolites provides insight into the complex relationship between HPA axis function and BMI

Aims/objectivesAlthough considerable effort, both experimental and theoretical, has been directed towards understanding the relationship between the HPA axis and weight regulation, no true consensus exists in the literature as to the nature of the relationship. The aim of this study was to explore potential correlations between BMI and measures of cortisol and cortisol metabolites using dried urine and saliva sampling in a large sample of individuals with BMIs ranging from underweight to obese. Materials and methodsA cohort of patients with data available from urinary and/or salivary measures of cortisol and cortisol metabolites who met inclusion criteria was extracted from the database of a commercial clinical laboratory. Pearson correlation coefficients were used to determine associations between variables; Student's t-test and one-way ANOVA were used to examine differences between groups, and the Jonckheere-Terpstra trend test was used to assess for trends by BMI category. A multivariable linear regression model was created to determine which variables explained the largest amounts of variance in BMI. ResultsA significant correlation was observed between the urinary cortisol metabolites and BMI (P < 0.0001). In addition, cortisol metabolites were associated with changes in BMI over time. No significant correlation was observed between urinary free cortisol and BMI, and correlations observed between BMI and other variables, with the exception of age, were either weak or not statistically significant. ConclusionsThe data presented in this study suggest that cortisol metabolism is a key component of weight regulation and that cortisol metabolite concentrations may potentially serve as informative biomarkers to characterize the relationship between the HPA axis and changes in BMI. The implications of this affect both clinical practice and the research and development of both prevention and treatment strategies aimed at either decreasing or increasing BMI.

Effect of chronic unpredictable stress in female Wistar-Kyoto rats subjected to progesterone withdrawal: Relevance for Premenstrual Dysphoric Disorder neurobiology

Premenstrual Dysphoric Disorder (PMDD) is related to an abrupt drop in progesterone and impairments in the HPA axis that cause anxiety. Suffering persons report higher daily-life stress and anxiety proneness that may contribute to developing PMDD, considered a chronic stress-related disorder. Here, we explored the effect of chronic unpredictable stress (CUS) in rats subjected to progesterone withdrawal (PW) and evaluated gene expression of HPA axis activation in the stress-vulnerable Wistar-Kyoto (WKY) rat strain that is prone to anxiety. Ovariectomized WKY rats were randomly assigned to CUS or Standard-housed conditions (SHC) for 30 days. To induce PW, animals received 2 mg/kg of progesterone on day 25th for 5 days; 24 h later, they were tested using the anxiety-like burying behavior test (BBT). After behavioral completion, rats were euthanized, and brains were extracted to measure Crh (PVN) and Nr3c1 (hippocampus) mRNA. Blood corticosterone and vasopressin levels were determined. Results showed that PW exacerbated anxiety-like behaviors through passive coping in CUS-WKY. PW decreased Crh-PVN mRNA and the Nr3c1-hippocampal mRNA expression in SHC. CUS decreased Crh-PVN mRNA compared to SHC, and no further changes were observed by PW or BBT exposure. CUS reduced Nr3c1-hippocampal gene expression compared to SHC animals, and lower Nr3c1 mRNA was detected due to BBT. The PW increased corticosterone in SHC and CUS rats; however, CUS blunted corticosterone when combined with PW+BBT and similarly occurred in vasopressin concentrations. Chronic stress blunts the response of components of the HPA axis regulation when PW and BBT (systemic and psychogenic stressors, respectively) are presented. This response may facilitate less adaptive behaviors through passive coping in stress-vulnerable subjects in a preclinical model of premenstrual anxiety.

Are hair cortisol levels dependent on hair growth rate? A pilot study in rhesus macaques

Research incorporating the analysis of glucocorticoids, specifically cortisol, in hair samples has exploded over the past 10–15 years, yet factors contributing to the accumulation of cortisol in hair are not yet fully characterized. In particular, it is not clear whether cortisol accumulation in hair is dependent on hair growth rate, a possibility raised by prior rodent studies reporting glucocorticoid-mediated inhibition of hair growth. Using rhesus macaque monkeys (Macaca mulatta), an extensively studied nonhuman primate species, the present pilot study evaluated the hypothesis that hair cortisol accumulation is inversely related to hair growth rate (i.e., slower hair growth leading to elevated cortisol levels). Hair samples were collected from 19 adult female macaques and 17 infants (9 males) 3 months apart using a shave-reshave procedure from the same site below the posterior vertex of the scalp. The second hair samples were measured to the nearest millimeter (mm) for growth rate over the previous 3 months and assayed for hair cortisol concentrations (HCCs) using enzyme immunoassay. Because of the possibility of age-related differences in hair growth rate, correlational analyses were performed separately for adults and infants to determine whether HCC values were associated with growth rate in each age group. These analyses revealed that neither group displayed a significant correlation of HCCs with hair growth. The results additionally showed that overall, adults had a faster hair growth rate than infants and, as expected from previous studies, had lower HCCs than infants. Our results suggest that higher HCCs within the non-stress range do not result from cortisol-mediated inhibition of hair growth. Moreover, similarities between humans and macaque monkeys in both HPA axis regulation and hair growth rates argue that these findings are relevant for human hair cortisol studies. Extrapolation to other species in which the features of hair growth and the relevant regulatory mechanisms are less well understood should be done with caution.

Protective Effects of Oviductus Ranae Mediated HPA Axis Regulation on Depressive Model of Mice

Protective Effects of Oviductus Ranae Mediated HPA Axis Regulation on Depressive Model of Mice

PMON17 Impaired cortisol regulation in Myotonic dystrophy

Abstract Introduction - Myotonic dystrophy (MD) is the most common cause of adult-onset muscular dystrophy. It has impaired HPA axis regulation with exaggerated ACTH response to CRH mediated stimuli and abnormal cortisol metabolism. We present a case of myotonic dystrophy in a male with elevated cortisol levels. Case report - 54-year-old male with a past medical history of type 1 myotonic dystrophy (MD1) presented for evaluation of hypogonadism with complaints of feeling fatigued, progressive weakness of muscles. During the workup, he was noted to have elevated cortisol levels 30.2 mcg/dL (6-18.4) with elevated ACTH 220 pg/mL (10-48). Other notable lab results included low total testosterone levels of 231, 185 with elevated LH of 17.3 m IU/ml (2-9) and FSH 37.7 m IU/ml (1-12). Prolactin levels were minimally elevated to 21.4 ng/mL (4-15.2). On further inquiry, the patient did not have headaches or vision changes. The patient did not report weight gain, easy bruising, change in facial appearance. Physical exam was significant for bilateral gynecomastia and small testes. No cushingoid facies, abdominal stria, proximal myopathy was noted. Given elevated ACTH and cortisol levels, further laboratory data showed a lack of suppression of cortisol levels with 1 mg dexamethasone - cortisol 2.9 micro g/dL (&amp;lt;1.8), elevated midnight salivary cortisol - 0.130, 0.102 ug/dl (0.010-0.090), and normal 24-hour urine cortisol levels -15 mcg/24 hours. Discussion – Even though Cushing's disease is one of the differential diagnoses for the above case, high cortisol levels have been reported in MD. Few mechanisms suggested causing this abnormality are increased ACTH responsiveness to CRH-mediated stimuli and abnormal cortisol metabolism. Patients with MD have high pro-inflammatory (IL-1 and TNF-a) markers, which mediate the increased ACTH responsiveness to CRH-mediated stimuli centrally by stimulating the HPA axis.1 In addition, IL-6 chronically stimulates steroidogenesis from the adrenal gland, whereas TNF-α inhibits ACTH-induced adrenal steroid synthesis and increases 11BHSD1 activity. Along with the impaired HP axis, abnormal metabolism of cortisol also contributes to elevated cortisol levels. Increased activity of 11 BHSD1 has been hypothesized to cause impaired clearance of cortisol.2 Impaired diurnal variation for cortisol is also seen in MD with elevated 24-hour cortisol levels. Elevated cortisol levels as in our case can be a diagnostic dilemma given impaired cortisol regulation as seen in MD. References Åsa Johansson et.al. Abnormal Cytokine and Adrenocortical Hormone Regulation in Myotonic Dystrophy, The Journal of Clinical Endocrinology &amp; Metabolism, Volume 85, Issue 9, 1 September 2000, Pages 3169–76.Åsa Johansson et.al. Glucocorticoid Metabolism and Adrenocortical Reactivity to ACTH in Myotonic Dystrophy, The Journal of Clinical Endocrinology &amp; Metabolism, Volume 86, Issue 9, 1 September 2001, Pages 4276–83 Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Evaluation of maternal cortisol-to-highly sensitive C-reactive protein ratio and glucocorticoid receptor resistance at 11–14 weeks of pregnancy to predict pre-eclampsia

Background: Preeclampsia (PE) is a disorder of pregnancy with a worldwide prevalence of about 5-8% and 4.6% in India. It is the second leading cause of direct maternal and foetal adverse outcomes, resulting in about 50,000-60,000 deaths annually worldwide. Cortisol is a stress hormone, that suppresses the immune system and inhibits the production of pro-inflammatory substances to reduce inflammation. During pregnancy cortisol levels raise to three-fold of nonpregnant level by the third trimester, it is due to changes in HPA axis regulation, raised oestrogen levels and raised maternal CRH levels through placental secretion. Aims: The objective of this study is to evaluate the cortisol (CORT)-to-highly sensitive C-reactive protein (HS-CRP) ratio and glucocorticoid receptor resistance (GCR) in early pregnancy to understand the pathophysiology of pre-eclampsia (PE) and to test whether these parameters have a role in the prediction of PE. CO + RT: HS-CRP ratio evaluates the interrelationship between the hypothalamic–pituitary–adrenal axis (HPA-axis) and the inflammatory response system. It is a new concept and an integrated approach to understand the pathophysiology of PE. Materials and Methods: In this prospective case–control study, we recruited 250 healthy pregnant women at 11–14 weeks of pregnancy and followed them. Those who developed PE after the 20th week according to the American College of Obstetricians and Gynecologists guidelines were considered study participants and the remaining served as controls. CORT was estimated through the ELISA method and HS-CRP was measured by autoanalyser through the turbidimetric method. The CORT-to-HS-CRP ratio was calculated manually. GCR was measured indirectly through leucocytes subsets, neutrophil-to-lymphocyte ratio (NLR) and neutrophil-to-monocyte ratio (NMR); individual leucocytes were obtained from complete blood counts. Data were analysed using the SPSS version 20, Pearson's correlation test was used to correlate the results and receiver operator characteristic (ROC) was used to test the predictive capacity of parameters. Results: Low CORT: HS-CRP was associated with PE, having a significance of P &lt; 0.00, but it did not show any specificity and sensitivity under ROC. NLR and NMR were elevated in cases who developed PE, especially NMR with P &lt; 0.008. NMR showed good specificity and sensitivity under ROC with the area under curve 0.74, cutoff value is 23. Conclusion: Low CORT: HS-CRP ratio has an association with PE, the uncontrolled inflammation during early pregnancy in pregnant women who were destined to develop PE. This is due to low-CORT secretion due to dysregulation of the HPA-axis. GCR also has an association with PE, but it was not fully clarified. HS-CRP and NMR can be used to screen in early pregnancy for the prediction of PE.

Prader-Willi syndrome proteins NDN and MAGEL2 are implicated in HPA axis regulation

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

The use of traditional Chinese medicines in relieving exercise-induced fatigue.

Exercise-induced fatigue is a non-pathological fatigue and indicated by a reduction of muscle performance that is caused by excessive physical activity. It seriously affects the daily lives of people, in particular athletes, military personnel, and manual laborers. In recent years, increasing attention has been paid to improving the adverse effect of exercise-induced fatigue on people's daily activities. Thus, studies and applications of traditional Chinese medicines (TCMs) in relieving exercise-induced fatigue have become the focus because of their good curative effects with fewer side effects. This review aims to document and summarize the critical and comprehensive information about the biological processes of exercise-induced fatigue, and to know the types of TCMs, their active components, and possible molecular mechanisms in alleviating exercise-induced fatigue. The peripheral and central mechanisms that cause exercise-induced fatigue have been summarized. A total of 47 exercise-induced fatigue relief TCMs have been collected, mostly including the types of visceral function regulation and emotional adjustment TCMs. Polysaccharides, terpenes, flavonoids/polyphenols are demonstrated to be the major bioactive components. The underlying molecular mechanisms are mainly related to the improvement of energy metabolism, elimination of excess metabolites, inhibition of oxidative stress and inflammatory response, regulation of HPA axis and neurotransmitters. Although current results are obtained mostly from animal models, the clinic trials are still insufficient, and a very few TCMs have been reported to possess potential hepatotoxicity. These findings still offer great reference value, and the significant efficacy in relieving exercise-induced fatigue is impossible to ignore. This review is expected to give insights into the research and development of new TCMs-derived drugs and health care products in relieving exercise-induced fatigue.

Association of Post-Traumatic Stress Disorder (PTSD) in Children and HPA Axis Regulation

Over the past decades, numerous findings have shown that exposure to stress or trauma during the critical period of early development can elicit adverse impacts on the psychological processes and physiological functioning of the body. Precisely, early life stress is associated with a greater risk of developing mental disorders or physical conditions later in life. Accordingly, early life adversity may alter children’s regulation of secretion of neurobiological substrates, as well as influence the sensitivity of their response to stimuli such as stressors. Children who encountered a traumatic event, such as natural disasters, sexual or physical abuse, may develop Post-traumatic stress disorder (PTSD), which may in turn disturbed the development of HPA axis and other neuroendocrinal systems which regulate the body’s response to stressors. However, the degree and manner of which childhood stress impacts the regulation of the HPA axis remain unclear and conflicted. Several studies have reported that abused children demonstrated substantially higher morning cortisol levels, which is regulated by the HPA axis, than non abused children. Other studies, however, have shown contradicting results Keywords: Adolescent, childhood trauma, corticotropins, cortisol, HPA axis regulation, post-traumatic stress disorder.

Consequences of Prematurity on Cortisol Regulation and Adjustment Difficulties: A 9-Year Longitudinal Study.

A preterm birth represents a stressful event having potentially negative long-term consequences. Thirty-three children born preterm (<33 weeks gestational age) and eleven full-term children participated in a nine-year longitudinal study. Perinatal Risk Inventory (PERI) was used at birth to assess the perinatal stress. Salivary cortisol, collected four times a day over two consecutive days, was measured with radioimmunoassay technique at six months and nine years to assess the hypothalamic-pituitary-adrenal (HPA) axis. Mothers reported post-traumatic symptoms on a self-report questionnaire 12 months after their child’s birth and children’s adjustment problems at 9 years of child age on the Child Behavior Checklist. Results showed a significant difference in cortisol regulation at nine years between preterm and full-term children but no differences in adjustment problems. Whereas biological factors (i.e., PERI, cortisol regulation at six months) explained cortisol at nine years, maternal post-traumatic symptoms were predictive of adjustment problems in their child. In conclusion, very preterm birth has some long-term consequences on the HPA-axis regulation at nine years. Although cortisol regulation is mostly influenced by biological factors, the presence of maternal post-traumatic symptoms predicts the manifestation of adjustment problems in both groups. This shows the importance of maternal psychological well-being for child development. Further research is needed to understand the exact consequences of premature birth on cortisol regulation and the implication for the child’s development and health.

Role of NR3C1 and SLC6A4 methylation in the HPA axis regulation in burnout

BackgroundWork-related stress and burnout have become major occupational health concerns. Dysregulation of HPA axis is considered one of the central mechanisms and is potentially moderated through epigenetics. In the present study, we aim to investigate epigenetic regulation of the HPA axis in burnout, by focusing on salivary cortisol and cortisone and DNA methylation of the glucocorticoid receptor gene (NR3C1) and the serotonin transporter gene (SLC6A4). MethodsWe conducted a cross-sectional study with 59 subjects with burnout and 70 healthy controls recruited from the general population. All participants underwent a clinical interview and psychological assessment. Saliva samples were collected at 0, 30 and 60 min after awakening and were used to quantify cortisol and cortisone. Pyrosequencing was performed on whole blood-derived DNA to assess DNA methylation. ResultsThere were no between-group differences in cortisol levels, whereas burnout participants had higher levels of cortisone. Job stress was associated with increased cortisol and cortisone. We observed both increased and decreased NR3C1 and SLC6A4 methylation in the burnout group compared to the control group. Some of these methylation changes correlated with burnout symptoms dimensionally. Increased methylation in a specific CpG in the SLC6A4 promoter region moderated the association between job stress and burnout. DNA methylation in this CpG was also associated with increased cortisol. In addition, average methylation of NR3C1 was negatively associated with cortisone levels. LimitationsThis is a cross-sectional study and therefore no conclusions on causality could be made. ConclusionsWe provide first evidence of changes in DNA methylation of NR3C1 and SLC6A4 in burnout, which were further associated with cortisol and cortisone. Further, increased cortisol and cortisone seemed to reflect job stress rather than burnout itself.

3-O-Acetyl-11-keto-β-boswellic acid ameliorates chronic unpredictable mild stress induced HPA axis dysregulation in relation with glutamate/GABA aberration in depressive rats.

Overt expression of brain glucocorticoid receptor (GR) leads to elevation of glutamate release causes cerebral excitotoxicity which in turn produce neuropsychological disorders. The aim of our work is to study the consequence of 3-O-Acetyl-11-keto-β-boswellic acid (AKBA) on chronic unpredictable mild stress (CUMS) induced HPA axis dysregulation in relative to glutamate and GABA irregularity in depressive rats. AKBA (5, 10 &15mg/kg) was administered for 28days parallel with CUMS induction in rats. Behavioural studies, tail suspension test (TST), open field exploratory (OFT) and forced swim test (FST) were performed. Biochemical studies including plasma corticosterone, glutamate GABA and glutamic acid decarboxylase (GAD) enzyme activity were studied. Glucocorticoid receptor expression and brain histology were studied to observe the effect of AKBA. CUMS induction results in depressive state of the animals were confirmed by the sucrose preference test. The administration of AKBA significantly reduced the immobility time and improved the exploratory behaviour. Plasma corticosterone and brain glutamate level was decreased and GABA level were increased significantly evident with GAD activation in AKBA-treated animals, further confirmed with decreased GR expression improves architecture of prefrontal cortex region. Correlation study illustrates behavioural improvements undeviating the biochemical alteration and GR expression after AKBA treatment during depression. AKBA significantly reversed the CUMS-induced glutamate/GABA abnormalities through the adaptation of central HPA axis regulation. Hence this study concludes that AKBA can be a better alternative to treat depressive disorders.

Effects of weariness of life, suicide ideations and suicide attempt on HPA axis regulation in depression

The neuropathological mechanisms leading to suicidality are still unknown, which, in view of an annual toll of around 1 million completed suicides constitutes an urgent clinical and societal problem. Alterations of stress hormone (ACTH and cortisol, representing the activity of the hypothalamic-pituitary-adrenocortical, HPA axis) regulation has been repeatedly studied in context of suicidality. Following a suicide attempt, stress hormone activity seems to be blunted, while depressed patients with suicidal ideation often present with elevated HPA axis activity. MethodsWe investigated the effects of different forms of suicidality on HPA axis regulation in 568 hospitalized patients of the Munich Antidepressant Response Signature (MARS) project. All patients had a diagnosis of a depressive disorder; 62 patients reported a recent suicide attempt, 192 patients suicide ideation, and 171 patients expressed weariness of life as the weakest form of suicidality, the latter not being analyzed in studies so far. All patients participated in the combined dexamethasone/corticotropin releasing hormone (dex/CRH) test for assessing HPA axis regulation shortly after admission to the hospital. ResultsWe found an increased ACTH and cortisol response following the dex/CRH-test in patients that were weary of life. In contrast, stress hormone response in suicide attempters and suicide ideators did not differ from non-suicidal patients. Further, repeated suicide attempts in patients’ history were associated with more pronounced stress hormone attenuation. ConclusionIn this so far largest study analyzing the HPA axis with respect to suicidality, we could not confirm the assumption of a general attenuation of HPA axis response in depressed suicide ideators and attempters. Conversely, HPA axis appears to be influenced by divergent effects of a specific suicidal psychopathology as well as outlasting effects of previous suicide attempts. We discuss these findings in the light of recent concepts of suicidality, pointing to multifactorial effects of acute and predisposing conditions on HPA axis reactivity in depressed patients.

Disaster-related prenatal maternal stress, and childhood HPA-axis regulation and anxiety: The QF2011 Queensland Flood Study

BackgroundThe fetal programming hypothesis suggests that prenatal maternal stress (PNMS) influences aspects of fetal development, such as the Hypothalamic Pituitary Adrenal (HPA) axis, enhancing susceptibility to emotional problems. No study (to our knowledge) has investigated this pathway considering development of preschool anxiety symptoms.Using data from the Queensland Flood study (QF2011), our objective was to determine whether toddler HPA-axis functioning mediated the association between aspects of flood-related PNMS and child anxiety symptoms at 4-years, and whether relationships were moderated by the timing of the stressor in utero or by the child’s sex. MethodsWomen, pregnant during the 2011 Queensland floods (N = 230), were recruited soon afterwards and completed questionnaires regarding their objective hardship (e.g., loss of personal property), subjective distress (post-traumatic-like symptoms) and cognitive appraisal of the disaster. At 16 months, indexes of the child’s diurnal cortisol rhythm (awakening response, total daily output, diurnal slope [N = 80]), and stress reactivity (N = 111), were obtained. At 4-years, N = 117 mothers reported on their own mood and their children’s anxiety symptoms; of these, N = 80 also had valid child cortisol reactivity data, and N = 64 had diurnal cortisol rhythm data. ResultsA greater cortisol awakening response at 16 months mediated the relationship between subjective PNMS and anxiety symptoms at 4-years. Greater toddler daily cortisol secretion predicted more anxiety symptoms, independent of PNMS. The laboratory stressor did not elicit a cortisol response. PNMS effects were not dependent upon child sex nor on gestational timing of flood exposure. ConclusionsIndexes of diurnal cortisol in toddlerhood may represent vulnerability for anxiety symptoms in preschoolers, both independent of, and following, exposure to disaster-related prenatal maternal subjective distress.

Effects of Nocturnal Sleep Quality on Diurnal Cortisol Profiles and Attention in Nurses: A Cross-Sectional Study.

Low sleep quality (LSQ) activates the hypothalamic-pituitary-adrenal (HPA) axis and is related to arousal. Nursing staff, who work in shifts, tend to exhibit LSQ, which affects the level of vigor after awakening. This study investigated the effects of nocturnal sleep quality on diurnal cortisol profiles and sustained attention in day-shift nurses. This study adopted a prospective cross-sectional design. Participants were recruited from a university-affiliated hospital in northern Taiwan. In the initial stage of this study, the Chinese Pittsburgh Sleep Quality Index (PSQI) Questionnaire was administered to 199 participants to categorize them as either LSQ (PSQI > 5) or high sleep quality (HSQ; PSQI ≤ 5). Participants were then randomly sampled from the two groups. Nocturnal sleep data and four diurnal saliva samples were collected for each participant. Sustained attention was measured before they started work. A total of 32 and 29 participants in the HSQ and LSQ groups, respectively, completed the data collection process. Compared with the HSQ group, the LSQ group exhibited earlier wake-up times (p = .02), a flatter cortisol awakening response (CAR) slope (p < .01), a flatter morning-to-evening slope (p < .01), and prolonged reaction speed and mean reaction time before starting work (p < .01). Compared with the HSQ group, the LSQ group exhibited impaired HPA-axis regulation, with a flatter CAR and diurnal cortisol slope and poor sustained attention in the morning. Nursing staff are advised to achieve HSQ to improve attention and performance levels and maintain optimum work safety.

SAT-387 Hypothalamic-Pituitary-Adrenal Axis in Elderly Women with Memory Impairment

Daily stress and aging have been associated with detrimental effects on memory. However, the role of lifestyle on the HPA axis regulation remains unclear.The aim of this study was to evaluate the relationship between lifestyle, memory and the HPA axis feedback regulation in aging women. Seventy women aged 65-87 y/o who complained of poor memory were interviewed, 30 of them met the inclusion criteria (absence of dementia, stroke, general anesthesia during the last year, endogenous depression, renal and hepatic insufficiency, drug or alcohol abuse and any medication that may affect the HPA axis). Only 28 completed the study. They obtained whole saliva samples to evaluate the daily rhythm of salivary cortisol (SAF) at 8.00 (SAF8), 16.00(SAF16) and 23.00 H (SAF23). The sensitivity of the HPA axis was assessed by the overnight 0.5 mg dexamethasone suppression test (DST). SAF and salivary dexamethasone (saD) after DST were determined at 8.00 (SAF8dex,saD8) and at 16.00 (SAF16dex,saD16). Reference values from our laboratory are: SAF8 ≤ 18.0 nM, SAF16 ≤ 6.0 nM, SAF23 ≤ 3.8 nM; SAF8dex and SAF16dex≤2.0nM, saD≥0.229 nM. Lifestyle (LS) and quality of life (QL) were evaluated by self-administered questionnaires (LS and SF36, respectively). Episodic, working and semantic memories, visuospatial perception and attention were also assessed. The protocol was approved by the Ethics Committee of IDIM A. Lanari and all subjects gave their written informed consent. SAF and saD were determined by RIA and ELISA, respectively. Statistics were performed by SPSS (p <0.05 was considered significant). Three patients did not suppress salivary cortisol (Sup-) at 8.00 and 16.00 H (SAF8dex: 10.6 ± 6.8nM and SAF16dex: 4.2±1.3nM); while 25 suppressed normally (Sup+). saD was not different between both groups. All subjects kept normal SAF diurnal variation although the slope was significantly less steep in Sup-(p<0.0001). Lifestyle index was significantly lower in Sup- than in Sup+, p=0.02, while there were no differences in QL. Thirteen out of 28 patients showed mild cognitive impairment (MCI). Among the MCI patients only the Sup- group had inadequate performance in 4 sections of the Rey Auditory Verbal Learning Test. Brain RMN performed in 2 Sup- showed enlargement of the sphenoidal extension of the lateral left ventricle that could be related to shrinkage of the ipsilateral medial temporal lobe. These findings suggest that DST might become a non-invasive approach to detect hippocampal damage in aging women with MCI.

Does sex hormone treatment reverse the sex-dependent stress regulation? A longitudinal study on hypothalamus-pituitary-adrenal (HPA) axis activity in transgender individuals

BackgroundStudies in mammals indicate a role for sex hormones in the regulation of hypothalamic–pituitary–adrenal (HPA)-axis reactivity. However, in humans, experimental paradigms investigating long-term exposure to sex hormones are sparse, limiting the understanding of the influence of sex hormones on HPA-axis activity. Gender-affirming hormone therapy (GAHT) in transgender persons enables to study the physiological role of sex steroids partially uncoupled from the distinct genetic background of men and women. MethodsTen transwomen (male genotype and female gender identity) and 15 transmen (female genotype and male gender identity) were investigated at baseline and following three months of GAHT by means of the combined dexamethasone (dex)/CRH-test. Linear mixed-effects model analysis was used to assess changes over time and to identify determinants of HPA-axis reactivity. ResultsIn response to CRH, overall ACTH (+18%) as well as cortisol (+15%) output were increased in transwomen after 3-months of estrogen and antiandrogen treatment, while the opposite was the case for transmen after testosterone treatment (-15% and -58%, respectively). The ACTH/Cortisol-ratio indicated that testosterone attenuated sensitivity for ACTH at the adrenal level in transmen. Interestingly, copeptin levels before CRH administration were a strong predictor of overall cortisol secretion. ConclusionsThis is the first study demonstrating long-term effects of a complete reversal of the sex-hormonal milieu on HPA-axis activity in humans. Our findings hereby expand the current knowledge of the physiology of HPA-axis regulation. and may be particularly relevant for transgender and cisgender people undergoing hormonal suppression or substitution therapies.

Ablation of glucocorticoid receptor in the hindbrain of the mouse provides a novel model to investigate stress disorders

The hypothalamic-pituitary-adrenal (HPA) axis regulates responses to internal and external stressors. Many patients diagnosed with conditions such as depression or anxiety also have hyperactivity of the HPA axis. Hyper-stimulation of the HPA axis results in sustained elevated levels of glucocorticoids which impair neuronal function and can ultimately result in a psychiatric disorder. Studies investigating Glucocorticoid Receptor (GR/NR3C1) in the brain have primarily focused on the forebrain, however in recent years, the hindbrain has become a region of interest for research into the development of anxiety and depression, though the role of GR signalling in the hindbrain remains poorly characterised. To determine the role of glucocorticoid signalling in the hindbrain we have developed a novel mouse model that specifically ablates hindbrain GR to ascertain its role in behaviour, HPA-axis regulation and adrenal structure. Our study highlights that ablation of GR in the hindbrain results in excessive barbering, obsessive compulsive digging and lack of cage exploration. These mice also develop kyphosis, elevated circulating corticosterone and severe adrenal cortex disruption. Together, this data demonstrates a role for hindbrain GR signalling in regulating stress-related behaviour and identifies a novel mouse model to allow further investigation into the pathways impacting stress and anxiety.

Telomere length and salivary cortisol stress reactivity in very preterm infants

During the Neonatal Intensive Care Unit (NICU) stay, very preterm (VPT) infants are exposed to life-saving yet pain-inducing skin-breaking procedures (i.e., NICU pain-related stress) which contribute to the programming of hypo-responsive HPA axis development during the first months of life. Unfortunately, to date the mechanisms linking NICU pain-related stress and altered HPA axis regulation are only limitedly known. Telomere length (TL) regulation is an epigenetic mechanism previously shown to be affected by early stress exposures and capable of associating with HPA axis reactivity in children. In VPT infants, NICU pain-related stress was found to associate with decreased TL from birth to discharge, but there is no evidence for the association between TL and HPA axis in these infants. In this study, we prospectively examined the relationship between NICU pain-related stress and HPA axis reactivity to an age-appropriate socio-emotional condition (i.e., the Still-Face Procedure, SFP) in healthy VPT infants at 3-month corrected age. NICU pain-related stress was computed as the ratio between the number of skin-breaking procedures and length of NICU stay. A differential score (i.e., ∆TL) was obtained subtracting TL at birth from TL at discharge. A normalized (log10) cortisol reactivity index (CRI) was obtained by averaging post-stress (20 min after SFP) salivary cortisol sample on baseline value. A regression model controlling for neonatal and socio-demographic confounders showed that ∆TL was the only significant predictor of CRI. Although preliminary, these findings contribute to our knowledge of the mechanisms linking early exposures to adversity and later in life regulation of the HPA axis in VPT infants.