Differences In Cortisol Responses Research Articles

Shaped by you: The effect of social partner on cortisol and behavior during adolescence in a female rodent

AbstractAdolescence is a sensitive phase when cues from the social environment can shape consistent individual differences in behavioral and hormonal profiles, but the effect of the social partner on these phenotypes is not well‐understood, especially for females. We therefore aimed to investigate whether the age class and sex of the housing partner affect social behavior and cortisol concentrations in female guinea pigs during adolescence and estimate the repeatability of cortisol concentrations in this life stage. Female guinea pigs were housed upon weaning for 4 weeks with either an adult female, adolescent female, or adolescent male. Social behavior was observed in the home enclosure and a preference test and social interaction test were carried out at the end of the experiment. Cortisol concentrations (baseline and response to a challenge) were measured prior to the start of the experiment and 2 and 4 weeks after pair formation. We hypothesized that the social partner would affect behavior and cortisol concentrations. We found that females housed with an adult female were less aggressive and more consistently displaced by their housing partner than females housed with an adolescent female. Sex of the housing partner did not affect focal female behavior. Regarding hormones, baseline cortisol concentration was neither significantly repeatable nor significantly affected by the housing partner. However, cortisol responsiveness was highly repeatable both 1 h and 2 h after the onset of a challenge. The age class of the housing partner affected cortisol responsiveness, with higher cortisol concentrations measured at 1 h in females housed with an adult female. These results indicate that adolescent female guinea pigs exhibit consistent individual differences in cortisol responsiveness while retaining plasticity to adjust to cues from the social environment. Taken together, we show in a female rodent that the social environment can significantly shape behavioral and endocrine parameters during adolescence.

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.

Cortisol reactivity impairs suppression-induced forgetting

To some extent, we can shape our recollections by intentionally remembering certain experiences while trying to forget others, for example, by intentional suppression. Acute stress impairs suppression-induced forgetting of memories. It is unclear, however, whether these deficits are a direct consequence of the acute stress-induced cortisol response. The present study was designed to examine the stress-induced impairment in suppression-induced forgetting in a subgroup of cortisol responders. We exposed healthy participants to a stress (n = 55) or no-stress control (n = 32) version of the Maastricht Acute Stress Test before they performed the Think / No-Think task. Here, participants aimed to repeatedly retrieve or suppress memories of previously learned cue-target video clips to mimic the complexity of episodic memories. Results on the subsequent memory test revealed that, while the no-stress controls and cortisol non-responders demonstrated suppression-induced forgetting, this effect was absent in cortisol responders. Moreover, the magnitude of suppression-induced forgetting was negatively correlated to stress-induced cortisol increases. The current study extends findings on stress-induced impairments in suppression-induced forgetting by specifically focusing on cortisol reactivity. Furthermore, our findings show the importance of individual differences in cortisol responses as a driving mechanism behind stress-induced alterations in our capacity to actively control our memory.

Endogenous cortisol-related alterations of right anterior insula functional connectivity under acute stress

BackgroundPrevious studies have suggested that the right anterior insula (rAI) plays a vital role in salience processing and stress-related disorders. In this study, we aimed to investigate the relationship between rAI functional connectivity changes and individual differences in cortisol responses after acute stress, in order to provide insights into psychiatric illness vulnerabilities. MethodsThirty-five young men were enrolled in a randomized, counterbalanced two-session study, with aversive movie clip combined with electrical shocks as stress stimulation and the neutral movie clip as control stimulation. Resting-state fMRI data was acquired after movie exposure. The rAI was chosen as seed for functional connectivity analysis. We then examined the effect of acute stress on rAI functional connectivity and its association with individuals’ cortisol response. ResultsWe found decreased rAI functional connectivity in the fronto-parietal regions, but increased functional connectivity in the visual and somatosensory areas following acute stress. Moreover, stress-induced cortisol response was significantly positively correlated with the rAI functional connectivity in the medial prefrontal cortex, and negatively correlated with the orbital-frontal cortex, lingual gyrus, and middle temporal gyrus. LimitationsOnly young Chinese males without any trauma experience were recruited in this study. ConclusionsThe results suggested tight link between specific rAI functional connectivity alterations and individual stress reactivity, which may help elucidate the potential neurobiological mechanism underlying vulnerability to stress-related disorders.

Individual differences under acute stress: Higher cortisol responders performs better on N-back task in young men

Exposure to stress has a variety of consequences on human behavior and cognition. Although widely investigated, the impact of stress on working memory remains inhomogeneous. Individual differences in neuroendocrine responsiveness, for example, cortisol responses, may be factors that explain previous inconsistent results. This study assessed the role of cortisol responsiveness in the effects of psychosocial stress on working memory. To examine working memory processes, we analyzed both behavioral performances such as accuracy, response time, the inverse efficiency score, and event-related potentials (ERPs), including N1, P2, and P3. A total of 67 male college students completed a numerical 2-back task after being exposed to the Trier Social Stress Task (TSST) or a control task. The results showed shorter response time, better efficiency, and larger N1 and P2 amplitudes in the high-cortisol-responders compared to the low-cortisol-responders and the control group. This indicates a better working memory performance likely due to the enhancements in the orientation and mobilization of attention. Furthermore, a correlation analysis revealed a positive association between the cortisol change rate and the working memory performance and ERP data among the stressed individuals, suggesting that increased cortisol may facilitate working memory under acute psychosocial stress. These findings emphasize that the individual differences in cortisol responses may affect the impact of stress on working memory.

Regulation of divergent cortisol responsiveness in European sea bass, Dicentrarchus labrax L.

Mechanisms regulating differences in cortisol responsiveness between low (LR) and high response (HR) individuals have been poorly studied. In this context, we aimed to study key regulatory processes in cortisol dynamics at the head kidneys of LR and HR European sea bass. To do so, resting plasma cortisol and ACTH concentrations were quantified in these fish. Additionally, the head kidneys of these individuals were superfused through an in vitro superfusion system and stimulated with the same amount of ACTH to assess their cortisol biosynthetic capacity. Moreover, the expression of important genes in cortisol regulation was assessed. Results showed that LR fish had lower resting cortisol concentrations than HR, although no differences existed in the circulating levels of ACTH. Additionally, the biosynthetic capacity of HR was higher than that of LR fish when in vitro stimulated with ACTH. At the molecular level, a statistically significant 3.4-fold higher expression of the ACTH receptor, mc2r, and a 2.3-fold, though not significant, higher expression of 11β-hydroxylase (cyp11b1), an enzyme involved in cortisol biosynthesis, was observed in the HR fish. Finally, a statistically significant 1.3-fold lower expression of 11β-hydroxysteroid dehydrogenase 2 (hsd11b2), an enzyme involved in cortisol inactivation, was observed in HR when compared to LR fish. Therefore, it was for the first time indicated that cortisol dynamics can also be regulated at the post-production level in the head kidney. Collectively, our results highlight the crucial role of the interrenal tissue in the regulation of differences in cortisol response between LR and HR sea bass individuals.

Differences in Cortisol Response to Trauma Activation in Individuals with and without Comorbid PTSD and Depression.

Background: Although depression symptoms are often experienced by individuals who develop posttraumatic stress disorder (PTSD) following trauma exposure, little is know about the biological correlates associated with PTSD and depression co-morbidity vs. those associated with PTSD symptoms alone.Methods: Here we examined salivary cortisol responses to trauma activation in a sample of 60 survivors of the World Trade Center attacks on September 11, 2001. Participants recalled the escape from the attacks 7 months post 9/11. Salivary cortisol levels were measured before and after their recollection of the trauma. PTSD, depression, and somatic symptoms were also assessed. From the behavioral assessment scales, the participants were grouped into three conditions: those with comorbid PTSD and depressive symptoms, PTSD alone symptoms, or no-pathology.Results: Baseline and cortisol response levels differed between the comorbid, PTSD alone, and no-pathology groups. Individuals endorsing co-morbid symptoms had higher PTSD and somatic symptom severity and their cortisol response decreased following their trauma reminder while a trend of an elevated response to the trauma was found in the PTSD alone group. Our findings show distinct psychological and biological correlates related to the endorsement of PTSD with and without depression comorbidity.Conclusions: The findings suggest that comorbidity symptoms manifestation entails a separate trauma induced condition from PTSD. Future research on biological correlates of comorbid PTSD and depression is warranted.

Salutary effects of an attention bias modification mobile application on biobehavioral measures of stress and anxiety during pregnancy

Stress and anxiety during pregnancy are associated with a range of adverse health outcomes, but there is an unmet need for low-barrier treatments that target stress and anxiety. One such treatment approach, attention bias modification training (ABMT), targets the anxiety-related threat bias, a disruption in attention to and neural processing of threat-related information. It remains unclear, however, whether reducing treatment barriers via mobile delivery of ABMT is effective and whether ABMT efficacy varies depending on individual differences in neural processing of threat. The present study tested whether mobile, gamified ABMT reduced prenatal threat bias, anxiety and stress, and whether ABMT efficacy varied with individual differences in neural responses to threat. Participants were 29 women in their 19th–29th week of pregnancy, randomized to four weeks of an ABMT or placebo training (PT) version of the mobile app using a double-blind design. Self-report of anxiety, depression, and stress were obtained; salivary cortisol was collected at home and in lab in response to stressors to index biological stress reactivity. Threat bias was measured using a computerized attention assay during which EEG was recorded to generate event-related potentials (ERPs) to threat cues. Results showed lower levels of lab cortisol following ABMT versus PT. Although the main effect of ABMT on subjective anxiety was not significant, the magnitude of cortisol reduction was correlated with lower levels of subjective anxiety and threat bias. Those receiving ABMT also reported less anxiety when showing smaller ERPs to threat (P1, P2) prior to training, but, conversely reported more anxiety when showing larger ERPs to threat. Use of gamified, mobile ABMT reduced biobehavioral indices of prenatal stress and anxiety, but effects on anxiety varied with individual differences in cortisol response and neurocognitive indices of early attention to threat.

The impact of acute stress on cognitive functioning: a matter of cognitive demands?

ABSTRACTIntroduction: There is a controversy in the literature whether stress and related cortisol responses are beneficial or impairing for cognitive functioning. Conflicting results might be due to individual differences in stress reactivity and cognitive load of the applied tasks.Methods: N = 48 participants underwent the Socially Evaluated Cold Pressor Test and were confronted with the Frankfurter Aufmerksamkeits-Inventar-2 (FAIR-2) which is a low-load attention task and two subscales of the Intelligenz-Struktur-Test 2000 R (I-S-T 2000R) as a high-load reasoning task before and after the stressor. Participants were post hoc divided into high (stress induced cortisol increase of ≥1.5 nmol/l) vs. low-cortisol responders.Results: Cortisol responders showed an increased attentional performance in the post-stress condition (η2 > .14). However, there were neither stress or responder main effects nor an interaction effect on reasoning abilities.Conclusions: Results of the present study show that stress related changes in cognitive performance are due to individual differences in cortisol response and the cognitive load of the performed task. Future studies will show if these results are also valid for alternative cognitive tasks and if they can be replicated in female participants.

The Diagnostic Approach to Central Adrenocortical Insufficiency (CAI) in Thalassemia.

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Tu1799 Differences in Cortisol Responses to Hormone Challenge vs. Visceral Stressor in Irritable Bowel Syndrome

Tu1799 Differences in Cortisol Responses to Hormone Challenge vs. Visceral Stressor in Irritable Bowel Syndrome

Cortisol response to the Trier Social Stress Test in pregnant women at risk for postpartum depression.

Antepartum depression and anxiety are risk factors for postpartum depression (PPD). Postpartum abnormalities in hypothalamic-pituitary-adrenal (HPA) reactivity are associated with PPD. It is not known if antepartum HPA abnormalities exist in women at risk for PPD (AR-PPD). We measured salivary cortisol response to the Trier Social Stress Test (TSST) in 44 (24 AR-PPD, 20 healthy comparison) pregnant women. Depression and anxiety were measured using the Edinburgh Postnatal Depression Scale (EPDS) and Spielberger State-Trait Anxiety Inventory-State (STAI-S). We analyzed longitudinal changes in cortisol using generalized estimating equation methods to control for the correlation within subjects at the six TSST time points. Group differences in area under the curve (AUC) were examined. A majority (70.8%) of the AR-PPD had prior depression. EPDS total score was higher in AR-PPD vs. comparison women (mean EPDS = 9.8 ± 4.9 vs. mean EPDS = 2.4 ± 2.0 respectively, p < 0.001). Mean STAI-S total score was higher in AR-PPD vs. comparison women at all TSST time points and over time (z = 2.71, df = 1, p = 0.007). There was no significant difference in cortisol concentration over time between groups. We observed no detectable difference in cortisol response to psychosocial stress induced by the TSST despite clinically significant between-group differences in current/past depression and current symptomatology.

Variability in HSP90AB1 and HSP90AA1 Are Not Correlated with Phenotypic Differences in Glucocorticoid Receptor‐Mediated Response or Subcellular Hsp90 Localization

Hsp90 is a highly conserved eukaryotic chaperone protein responsible for mediating a multitude of intracellular signaling molecules, including those associated with the glucocorticoid receptor (GR) and stress response. The goal of this study was to identify the extent to which single nucleotide polymorphisms (SNPs) in genes encoding hsp90 correlated with previously observed phenotypic variations in circulating cortisol and hsp90 subcellular localization. Salivary cortisol was measured in healthy volunteers before and after HPA stimulation via mild cardiovascular stress. Whole exome sequencing of a matched participant pair identified HSP90AB1, encoding the stress‐inducible isoform of hsp90, as a potential causal candidate gene warranting further examination. Exons of HSP90AB1 and HSP90AA1 were amplified and sequenced in 20 participants with known differences in cortisol response and hsp90 localization using PCR and the Sanger method. Out of the twenty participants, three HSP90AB1 and eight HSP90AA1 SNPs were found, all of which were registered in the NCBI SNP database. Interestingly, a discrepancy in results was observed between SNPs called by whole exome analysis and those detected by Sanger sequencing. Although no correlation was found between analyzed SNPs, cortisol response, and hsp90 localization, further work utilizing this methodology and consideration of phenotypic polygenicity will likely provide a more comprehensive understanding of hsp90‐mediated GR signaling.

A Study of Psychological Effects of Pilots Depending on the Different Environments between Actual and Simulated Flights

Objective: This study aims to examine the psychological effects of pilots caused by the environmental differences between actual and simulated flights by measuring biochemical stress level and subjective stress level.BRBR Background: Currently, the flight system of the air force suffers from several problems including a limited training area, increase of complex and tangled missions and rise in oil prices. In order to overcome these problems an L-V-C (Live, Virtual, Constructive) training system has been proposed as a solution. However, to establish the effective L-V-C training system, it is required to figure out the characteristics of each system first. Also we have to solve the problems which could occur when these systems are connected together.BRBR Method: In order to measure the biochemical stress level of pilots, we investigated the differences in cortisol responses after actual and simulated flight training separately. Meanwhile, we conducted the questionnaire survey of about 40 pilots to identify the subjective stress level of pilots.BRBR Results: There was significant difference in cortisol level between actual and simulated flight tasks. However, we found that there was no significant difference in pilots" feelings about two flight tasks.BRBR Conclusion: The results from this study can be used as basis for the further research on not only how to decrease linkage errors of the L system and the V system but also how to make the L-V training system more practical.BRBR Application: The results of the analysis might help to develop the Live-Virtual-Constructive (LVC) pilot training system.

Stress-induced behavioral and metabolic adaptations lead to an obesity-prone phenotype in ewes with elevated cortisol responses.

The underlying cause of predisposition to obesity is complex but one marker is cortisol responsiveness. Selection of sheep for high (HR) or low (LR) cortisol responses to adrenocorticotropin shows that HR are more likely to become obese. Increased propensity to obesity is associated with reduced skeletal muscle thermogenesis. We sought to determine whether metabolic or behavioral responses to stress also contribute to altered propensity to obesity in LR and HR. Animals (n=5-10/group) were exposed to 3 stressors and we measured food intake and thermogenesis (recorded with dataloggers implanted into muscle). Stressors were hypoglycaemia (0.125 units/kg insulin, IV), a barking dog and immune challenge (200 ng/kg lipopolysaccharide--LPS, IV). LR animals showed a greater catabolic state in response to both immune and psychosocial stressors. LPS reduced (P<0.01) food intake in both groups but LR showed a greater (P<0.05) reduction in food intake and a more substantial (P<0.05) rise in muscle temperature. Introduction of the barking dog reduced (P<0.05) food intake in LR only. These metabolic differences coincided with differences in cortisol responsiveness, where HR animals had increased (P<0.05) cortisol in response to both immune and psychosocial stressors. We also assessed behavior in the following paradigms: 1, isolation in the open field test; 2, response to a human intruder; and 3, food competition. LR had greater (P<0.05) activity, reduced fearfulness and displayed a proactive coping style of behavior. Thus we demonstrate that high cortisol responsiveness identifies animals with stress-induced metabolic and behavioral traits that may contribute to susceptibility to obesity.

Whole exome sequencing analysis of inter‐participant cortisol response: strategies for matching phenotype to genotype (983.1)

The overarching goal of this project is to identify genetic variants that are indicative of an individual’s systemic and intracellular responses to corticosteroids. We previously observed inter‐participant variability in cortisol and nuclear hsp90 concentrations following exposure to mild cardiovascular stress, which could not be attributed to demographic or lifestyle characteristics or to single nucleotide polymorphisms (SNPs) in the glucocorticoid receptor, hsp90, or CRHR1 genes. We conducted whole exome sequencing of matched participant pairs who displayed similar demographic and lifestyle characteristics yet possessed distinct cortisol response phenotypes. Using an Agilent V4 exome enrichment platform and Illumina HiSeq2000 paired end (2 x 100 bp) sequencing, &gt;44 million reads per sample were aligned to the hg19 reference build. This analysis resulted in average 30x coverage and combined analysis of &gt;440,000 base pair variants. We developed a bioinformatics analysis pipeline to compare datasets of matched participant samples to one another and against the NHLBI dataset of &gt;6,500 sequenced exomes. Filtering identified candidate causal variants associated with the phenotypic difference in cortisol response. These genes, which have the potential to impact corticosteroid‐mediated signaling and pharmacotherapy, are now being investigated for functional significance.Grant Funding Source: Supported by NIH AREA grant GM086822

Accelerometry and salivary cortisol response during Air Force Special Tactics Officer selection

BackgroundSpecial Tactics Officer (STO) selection is conducted to select officers to enter the combat controller training pipeline. The aims were to determine physical activity patterns, estimate energy expenditure, and identify whether return and/or unsuccessful candidates demonstrated differences in cortisol responses compared to non-selected and/or first-time attendees.MethodsParticipants completed the STO selection, consisting of 5 days of physical and mental challenges. Participants were equipped with ActiCals®, and saliva samples were collected throughout the STO selection.ResultsAverage activity counts were 684 ± 200 counts∙min−1, with no group differences. Estimated energy expenditure was 4,105 ± 451 kcal∙day−1. Cortisol was elevated following extended physical training but returned to baseline during rest. Return candidates had significantly lower cortisol responses compared to first-timers, 0.43 ± 0.06 μg∙dl−1 versus 0.76 ± 0.18 μg∙dl−1, respectively, p < 0.05.ConclusionsAn individual's salivary cortisol response to the stresses incurred during the STO selection has the potential to be incorporated into the entire picture of a candidate's performance and ability to handle stress.

Response of the hypothalamic-pituitary-adrenal axis to stimulation tests before and after exercise training in old and young Standardbred mares1

This study tested the hypotheses that age-induced alteration in cortisol, ACTH, and glucose concentrations are due to differences in the response of the hypothalamic-pituitary-adrenal axis and that exercise training would attenuate these differences. Six old (22.0±0.7 yr; mean±SE) and 6 young (7.3±0.6 yr) unfit Standardbred mares ran 3 graded exercise tests (GXT): before (GXT1), after 8 wk of training (GXT2), and at study end at 15 wk (GXT3). Mares trained 3 d/wk at 60% maximum heart rate. Each mare underwent 5 endocrine stimulation tests pre- and posttraining: 1) control (CON), 2) adrenocorticotropin hormone (ACTHtest), 3) combined dexamethasone suppression/ACTH (DEX/ACTH), 4) dexamethasone suppression (DEX), and 5) combined DEX/corticotropin releasing factor (DEX/CRF). For CON, there was no difference in plasma cortisol between age groups pretraining (P=0.19), but young mares had a 102% higher mean (P=0.02) plasma cortisol concentration than old mares posttraining. The pretraining ACTHtest showed young mares had a 72% higher (P=0.05) overall plasma cortisol concentration compared to old. There was no overall age difference in cortisol in the posttraining ACTHtest, but old mares still had lower cortisol concentrations at 30 min during the test, suggesting decreased adrenal response to ACTH stimulation. There was no difference in cortisol response between old and young mares in DEX, DEX/ACTH, or DEX/CRF tests. Young mares had higher (P=0.02) overall plasma cortisol concentration posttraining in response to DEX/ACTH, but old mares showed no change. In CON and DEX/CRF, there were no age differences in plasma ACTH concentration, pre- or posttraining. Pretraining, there was no age difference in glucose response to DEX, but posttraining old mares had a 4% (P=0.04) lower overall plasma glucose concentration compared to young. Posttraining, old mares had lower mean plasma glucose concentrations during DEX compared to pretraining (P=0.02), but there was no change pre- vs. posttraining in young mares (P=0.19). Old and young mares had lower plasma glucose concentrations posttraining during DEX/ACTH (P<0.001 and P=0.05, respectively) and DEX/CRF (P<0.001 and P=0.003, respectively) compared to pretraining. Both the pituitary and adrenal glands experience a decline in function with age although the exact mechanisms behind such changes remain unknown. Exercise training facilitates the counteraction of these deficits.

Quality of maternal and paternal care predicts later stress reactivity in the cooperatively-breeding marmoset (Callithrix geoffroyi)

Variation in the early postnatal social environment can have lasting effects on hypothalamic-pituitary-adrenal (HPA) axis stress responses. Both rats and macaque monkeys subjected to low quality or abusive maternal care during the early postnatal period have more pronounced HPA responses to environmental stressors throughout development and into adulthood compared to animals reared in higher quality early maternal environments. However, little is known about the relative contributions to HPA stress response styles in developing offspring in species in which offspring care is routinely provided by group members other than the mother, such as in cooperatively breeding mammals. Marmoset monkeys exhibit cooperative offspring rearing, with fathers and older siblings providing care in addition to that provided by the mother. We evaluated the effects of early maternal, paternal, and older sibling care on HPA responses to social separation across development in captive white-faced marmoset offspring (Callithrix geoffroyi). We monitored offspring care by mothers, fathers, and older siblings in marmosets for the first 60 days of life. Later in development, each marmoset experienced three standardized social separation/novelty exposure stressors at 6, 12, and 18 months of age. During separation, we collected urine samples and analyzed them via enzyme immunoassay for cortisol levels. Infants that received higher rates of rejections from the entire family group showed higher cortisol responses to social separation. This relationship was found when mothers, fathers, and older siblings, were analyzed separately as well. No differences in cortisol responses were found between offspring that received high and low rates of carrying or high and low rates of licking and grooming by any group member. In the cooperatively breeding marmoset, early social cues from multiple classes of caregivers may influence HPA stress responses throughout the lifespan.

Single nucleotide polymorphisms and subcellular localization of glucocorticoid receptor‐associated signaling proteins associated with cortisol‐mediated stress response

The goal of our study was to identify correlations between interpersonal genetic variability in healthy volunteers and alterations in the glucocorticoid receptor‐associated signaling pathway. Salivary cortisol (CORT) concentrations were measured in healthy volunteers (n=66) before and after CORT stimulation in order to determine variability in circulating CORT levels and CORT response. Statistical analysis revealed inter‐participant CORT variability in concentration or percent change were not exclusively correlated to participant demographics, health history, or glucocorticoid receptor (GR) single nucleotide polymorphisms (SNPs). Interestingly, nuclear localization of the GR‐associated molecular chaperone protein hsp90 correlated with an elevated pre‐stimulus CORT concentration. To investigate the observed CORT response‐hsp90 localization association further, coding and proximal coding regions of the constitutively expressed hsp90 gene (HSP90AA) were sequenced to identify a possible genetic linkage. Eight hsp90 SNPs were identified, four of which were not reported in the NCBI database. All participants expressed at least two of the hsp90 SNPs, with some participants exhibiting as many as five. These data demonstrate inter‐person differences in CORT response, nuclear hsp90 concentrations, and GR‐associated SNPs are readily detected and potentially interrelated.