Acculturation, childhood trauma and the cortisol awakening response in Mexican-American adults

Exposure to chronic and traumatic stress has been associated with the dysregulation of crucial stress response systems. Acculturation has been associated with unique forms of chronic psychosocial stress. The purpose of this study was to examine the effects of exposure to early traumatic stress and acculturation on dysregulation of the cortisol awakening response (CAR) in Mexican-American adults. Salivary cortisol samples were collected at awakening and 30, 45, and 60 min thereafter, on two consecutive weekdays from 59 healthy Mexican-American adult males (26) and females (33), ages 18-38 years. Participants were assessed for level of acculturation and exposure to early trauma. Data were analyzed using a mixed effects regression model with repeated measures at four time points. Mixed effects regression results indicated a significant Early Trauma × Time interaction (p = .0029) and a significant Acculturation × Time interaction (p = .0015), after controlling for age and sex. Subsequent analyses of the interaction of Trauma × Acculturation × Time showed that more than minimal exposure to either risk factor was associated with attenuation of the awakening cortisol response (p = .0002). Higher levels of acculturation with greater Anglo-orientation were associated with attenuation of the CAR in Mexican-American adults. Both moderate and higher levels of exposure to early trauma were associated with an attenuated CAR. However, greater exposure to both risk factors was only incrementally worse than exposure to either one.     

Negative relationships in the family-of-origin predict attenuated cortisol in emerging adults

Negative childhood family environments have been associated with stress-related physical and psychological health consequences across the lifespan. The present study examined the relation between adverse relationships in the family of origin and physiological stress response, as measured by salivary cortisol, in emerging adulthood. Seventy-six university students (age range = 18-22) selected from intact married families-of-origin characterized by either negative (n = 39) or positive (n = 37) relationship quality engaged in a challenging role play task. Results from multilevel models indicated that those from negative families exhibited significantly lower salivary cortisol across the task than those from positive families. This relation did not change in strength or direction after controlling for experiences with abuse or recent anxiety or depressive symptoms. These findings suggest the significance of early family relationships on the long-term activity of the HPA axis.     

The cortisol awakening response (CAR) in male children with autism spectrum disorder

Our ability to adapt to change is fundamental. The cortisol awakening response (CAR) is a sharp rise in cortisol 30 min after waking to help prepare an individual for ensuing stress. Children with autism spectrum disorder (ASD) often have difficulty adapting to change. Exploration of the CAR is warranted; yet, the few studies investigating it are inconclusive. The CAR was investigated in 94 pre-pubertal male children 8-to-12 years of age with ASD (46) and typical development (TD, 48). Salivary samples were collected over three diurnal cycles involving two morning samples: M1: Immediately upon Waking and M2: 30-min Post Waking (M2 − M1 = CAR). The magnitude of the CAR was measured by independent two sample t-tests, variability was measured using Levene's Test, the sequence of the CAR was analyzed by a linear mixed-effects model and proportion of children exhibiting a CAR by chi-square test of independence. There were no significant differences on the CAR between the groups based on magnitude (t(92) = − 0.14, p = 0.89, d = 0.04), variability (F(45,47) = 1.11, p = 0.72, η² = 0.11) or the sequence over three days (F(2,88) = 0.26, p = 0.77, η² = 0.01). No significant differences were shown in the proportion of children exhibiting a CAR across the groups based on child (χ²(1) = 0.02, p = 0.89) or adult criterion (χ²(1) = 1.82, p = 0.18). Despite group differences in the regulation and responsivity of cortisol, the CAR is indistinguishable between children with and without ASD. Inconsistencies across studies may be due to age, criterion used, and diagnostic distinctions.     

Diurnal salivary cortisol is associated with body mass index and waist circumference: The multiethnic study of atherosclerosis

Objective:

Neuroendocrine abnormalities, such as activation of the hypothalamic‐pituitary‐adrenal (HPA) axis, are associated with obesity; however, few large‐scale population‐based studies have examined HPA axis and markers of obesity. We examined the cross‐sectional association of the cortisol awakening response (CAR) and diurnal salivary cortisol curve with obesity.

Design and Methods:

The Multiethnic Study of Atherosclerosis Stress Study includes 1,002 White, Hispanic, and Black men and women (mean age 65 ± 9.8 years) who collected up to 18 salivary cortisol samples over 3 days. Cortisol profiles were modeled using regression spline models that incorporated random parameters for subject‐specific effects. Cortisol curve measures included awakening cortisol, CAR (awakening to 30‐min postawakening), early decline (30 min to 2‐h postawakening), late decline (2‐h postawakening to bedtime), and the corresponding areas under the curve (AUC). Body mass index (BMI) and waist circumference (WC) were used to estimate adiposity.

Results:

For the entire cohort, both BMI and WC were negatively correlated with awakening cortisol (P < 0.05), AUC during awakening rise, and early decline and positively correlated to the early decline slope (P < 0.05) after adjustments for age, race/ethnicity, gender, diabetes status, socioeconomic status, β‐blockers, steroids, hormone replacement therapy, and smoking status. No heterogeneities of effects were observed by gender, age, and race/ethnicity.

Conclusions:

Higher BMI and WC are associated with neuroendocrine dysregulation, which is present in a large population sample, and only partially explained by other covariates.     

Daily Life Stress and the Cortisol Awakening Response: Testing the Anticipation Hypothesis

The cortisol awakening response (CAR) is a distinct facet of the circadian cortisol rhythm associated with various health conditions and risk factors. It has repeatedly been suggested that the CAR could be a result of the anticipated demands of the upcoming day (stress anticipation) and could support coping with daily life stress. In a sample of 23 healthy participants CARs were assessed on two consecutive days by measures of salivary cortisol upon awakening (S1) and 30 and 45 minutes later, which were aggregated to the area under the curve increase (AUCI). Stress anticipation was assessed immediately after awakening. On the same days, daily life stress and distress were assessed six times per day based on a quasi-randomized design using handheld computers. Associations were tested by day using regression analysis and standard multilevel/mixed effects models for longitudinal data. The CAR AUCI moderated the effect of daily life stress on distress; higher CAR increases were associated with attenuated distress responses to daily life stress on both days (day 1: p = .039; day 2: p = .004) adjusted for age, gender, sleep quality, time of awakening and oral contraceptive use. Lagged-effects and redundancy models showed that this effect was not due to prior-day CAR increases but specific for same day CARs. On day 2, associations between daily life stress and distress were stronger when individuals showed a higher S1 cortisol level, but this effect was similar for S1 on day 1, and the day 2 effect of S1 became non-significant when S1 on day 1 was controlled. No associations were found between stress anticipation and CARs. Findings indicate that the CAR increase is associated with successful coping with same-day daily life stress.     

Prenatal exposure to maternal psychosocial stress and HPA axis regulation in young adults

Epidemiological studies have reported associations between measures of size and weight at birth and disease risk in later life. Alteration in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis in response to prenatal stress has been proposed as one underlying mechanism. The present study investigated in humans the association of prenatal psychosocial stress exposure with subsequent HPA axis regulation in adult life, with a focus on measures of response to challenge and feedback sensitivity. Healthy young adults whose mothers experienced severe stress during their pregnancy in form of major negative life events (e.g. death of someone close; prenatal stress (PS) group, n = 31) and an age-matched comparison group (CG, n = 30) underwent the Trier Social Stress Test (TSST) and a 1 μg ACTH_1-24 stimulation test. In addition, a diurnal cortisol profile was assessed. ACTH concentrations following a standardized behavioural challenge paradigm (TSST) were marginally significantly higher in PS subjects than in CG subjects (p = .06). Pre-TSST adrenocortical (cortisol) levels were lower (p = .007), whereas the increase in cortisol in response to the TSST was higher (p = .03) in PS subjects compared to CG subjects. Cortisol concentrations following a pharmacological stimulation test simulating pituitary activity (ACTH_1-24 test) were significantly lower in PS than in CG subjects (p = .006). No differences emerged between the two groups in basal diurnal cortisol levels. This study provides first evidence in humans of an association between prenatal psychosocial stress exposure and subsequent alterations in the regulation of the HPA axis.     

Relationship between change in core temperature and change in cortisol and TNFα during exercise

The combined thermal load created by exercise and a hot environment is associated with an exaggerated core temperature response. The elevated core temperature is believed to increase the total stress of the exercise. Increased stress during exercise has been associated with increased levels of cortisol. The association of cortisol with increased inflammatory responses following exercise in the heat is equivocal. Thus, the purpose of the current investigation was to explore the relationship between increases in rectal temperature (T_re) and TNFα and cortisol. To induce T_re changes, 8 male subjects (mean±SD, age=23.6±2 yr, VO₂max=52.8±3.7 mL/kg/min, BMI=24.2±1.9) participated in two 40 min trials of cycle ergometry at 65% of VO₂peak immersed to chest level in cool (25 °C) and warm (38.5 °C) water. T_re was monitored throughout each trial, with blood samples taken immediately pre and post of each trial. Neither cortisol nor TNFα changed significantly during exercise in the cool water; however, in the warm trial, both cortisol and TNFα significantly increased (p<0.004). Concordance correlations (R_c) between Δ cortisol and Δ TNFα indicated a strong but non-significant correlation (R_c=0.833, p=0.135). In conclusion, changes in core temperature may be impacting the relationship between exercise induced changes in cortisol and TNFα. Therefore, acute moderate-intensity exercise (40 min or less) in warm water impacts the stress and inflammatory response. Understanding this is important because exercise load may need to be adjusted in warm and hot environments to avoid the negative effects of elevated stress and inflammation response.     

Self-reported symptoms of depressed mood, trait anxiety and aggressive behavior in post-pubertal adolescents: Associations with diurnal cortisol profiles

The association between self-reported symptoms and diurnal cortisol profiles was studied in post-puberty adolescents (29 boys and 29 girls, M_age = 15.06 years). The adolescents completed the Children's Depression Inventory, State Trait Anxiety Inventory, and an Aggressive behavior scale. The diurnal cortisol profile was derived from three saliva samples, collected at awakening, noon and evening on a week-end day. Univariate repeated measurement regressions revealed that depressed mood and trait anxiety were strongly and aggressive behavior was weakly related to the diurnal cortisol profile: greater emotional distress was associated with flatter diurnal cortisol profiles. Multivariate analysis, however, revealed that only trait anxiety made an independent contribution. Further analyses suggested that trait anxiety was related to elevated evening cortisol rather than to decreased awakening cortisol and that from a trait anxiety score of 38 onwards, high anxious adolescents show clearly higher evening cortisol than low anxious adolescents. These data suggest that anxiety disorder co-morbidity might explain some of the differences in HPA-axis function among depressed patients.     

Abolished circadian rhythm of salivary cortisol in elite artistic gymnasts

Objective

The aim of this study was to evaluate the effects of intensive physical exercise and acute psychological stress during high level athletic competition as reflected on the levels of salivary cortisol in elite artistic gymnasts (AGs).

Design

The study included 239 AGs (142 females-97 males) who participated in the European Championship of Gymnastics in 2006 and 81 adolescents (40 females-41 males), matched for age, as controls. All athletes participated voluntarily in all or parts of the study, providing samples or data for each of the variables measured. Height, weight, body fat, lean body mass (LBM), bone age and Tanner stage of puberty were assessed and data concerning the time of thelarche, adrenarche and menarche as well as, the onset and the intensity (hours per week) of training were obtained.

Methods

Saliva samples were collected, the morning before training and in the afternoon shortly after the competition. From controls, the saliva samples were collected in the morning. Cortisol concentrations were measured using a chemiluminescence method. Acute stress was assessed using a questionnaire designed for the study.

Results

No difference was found between morning and afternoon salivary cortisol levels in both male and female AGs (females: AM: 15.45 ± 7.45 nmol/l vs PM: 15.73 ± 9.38 nmol/l; males: AM: 10.21 ± 5.52 nmol/l vs PM: 9.93 ± 13.8 nmol/l, p > 0.05).Female AGs presented higher levels of morning salivary cortisol than female controls (p < 0.05). Both male and female AGs had higher degree of psychological stress in comparison with controls (p < 0.001, p < 0.013, respectively). Female AGs had higher morning and afternoon salivary cortisol levels (p < 0.01, p < 0.01, respectively) and higher degree of stress (p < 0.003) than males.

Conclusions

In elite AGs the diurnal rhythm of salivary cortisol has been abolished, probably due to the strenuous training and competition conditions. Female AGs presented higher levels of morning salivary cortisol and psychological stress compared to both male AGs and female controls. The long term consequences of these modifications of the HPA axis remain to be elucidated.     

The effect of rearing experience and TPH2 genotype on HPA axis function and aggression in rhesus monkeys: A retrospective analysis

Gene-environment (G × E) interactions contribute to the development of many neuropsychiatric disorders. Tryptophan hydroxylase-2 (TPH2) synthesizes neuronal serotonin and is closely related to the hypothalamic-pituitary-adrenal (HPA) axis, while early life experience is a critical environmental factor programming the HPA axis response to stress. This retrospective study investigated G × E interaction at the TPH2 locus in rhesus monkeys. Twenty-eight adult, male rhesus monkeys of Indian origin, either mother-reared or peer-reared as infants, were involved in this study. These monkeys have been previously genotyped for the functional A2051C polymorphism in rhTPH2, and had been physiologically and behaviorally characterized. rhTPH2 A2051C exerted a significant main effect (CC > AA&AC) on the cerebrospinal fluid (CSF) level of 5-hydroxyindole-3-acetic acid (5-HIAA; F_(1,14) = 6.42, p = 0.024), plasma cortisol level in the morning (F_(1,18) = 14.63, p = 0.002) and cortisol response to ACTH challenge (F_(1,17) = 6.87, p = 0.018), while the rearing experience showed a significant main effect (PR > MR) on CSF CRH (F_(1,20) = 11.66, p = 0.003) and cage shaking behavior (F_(1,27) = 4.45, p = 0.045). The effects of rhTPH2 A2051C on the afternoon cortisol level, plasma ACTH level, dexamethasone suppression of urinary cortisol excretion, and aggression were dependent upon the rearing experience. These results were not confounded by the functional C77G polymorphism in the mu-opioid receptor (MOR). The present study supports the hypothesis that rearing experience and rhTPH2 A2051C interact to influence central 5-HT metabolism, HPA axis function, and aggressive behaviors. Our findings strengthen the involvement of G × E interactions at the loci of serotonergic genes and the utility of the nonhuman primate to model G × E interactions in the development of human neuropsychiatric diseases.     

Shiftwork Duration and the Awakening Cortisol Response Among Police Officers

Police officers are required to work irregular hours, which induces stress, fatigue, and sleep disruption, and they have higher rates of chronic disease and mortality. Cortisol is a well-known “stress hormone” produced via activation of the hypothalamic-pituitary-adrenal axis. An abnormal secretion pattern has been associated with immune system dysregulation and may serve as an early indicator of disease risk. This study examined the effects of long- and short-term shiftwork on the cortisol awakening response among officers (n = 68) in the Buffalo Cardio-Metabolic Occupational Police Stress (BCOPS) pilot study (2001–2003). The time each officer spent on day (start time: 04:00–11:59?h), afternoon (12:00–19:59?h), or night (20:00–03:59?h) shifts was summarized from 1994 to examination date to characterize long-term (mean: 14 ± 9 yrs) and short-term (3, 5, 7, or 14 days prior to participation) shiftwork exposures. The cortisol awakening response was characterized by summarizing the area under the curve (AUC) for samples collected on first awakening, and at 15-, 30-, and 45-min intervals after waking. Data were collected on a scheduled training or off day. The cortisol AUC with respect to ground (AUC_G) summarized total cortisol output after waking, and the cortisol AUC with respect to increase (AUC_I) characterized the waking cortisol response. Officers also completed the Center for Epidemiologic Studies Depression scale. Waking cortisol AUC values were lower among officers working short-term night or afternoon shifts than day shifts, with maximal differences occurring after 5 days of shiftwork. The duration of long-term shiftwork was not associated with the cortisol awakening response, although values were attenuated among officers with more career shift changes. (Author correspondence: burch@mailbox.sc.edu)     

Cell phenotyping in saliva of individuals under psychological stress

Total leukocytes, NK cells, B and T lymphocytes present in the saliva of medical students with or without stress were quantified by flow cytometry in 10,000 events. The symptoms of psychological stress were monitored with Lipp’s Inventory of Stress Symptoms for Adults (ISSL). No significant differences were observed in the number of cells phenotyped in students with and those without psychological stress. However, a negative correlation was observed between the number of NK cells and T lymphocytes in students with stress (r = −0.8173; p = 0.0058), suggesting that innate immunity is predominant in the adaptation phase.     

Influence of shift type on sleep quality of female nurses working monthly rotating shifts with cortisol awakening response as mediating variable

ABSTRACT

When shift nurses change shifts, it is likely to affect the cortisol patterns of their bodies and sleep quality. The objectives of this study was to verify the influence of monthly rotating day, evening and night shifts on the sleep quality of female nurses and determine whether the cortisol awakening response (CAR) mediates this relationship. A total of 132 female shift nurses were recruited, and ultimately 128 complete questionnaires and samples were obtained (subject loss rate = 3.0%) from 45 day-shift nurses, 44 evening-shift nurses and 39 night-shift nurses at a teaching hospital in Northern Taiwan. The Pittsburgh sleep quality index served as the research instrument that nurses used to collect saliva samples at home every day after waking and 30?min after waking so as to calculate the net increases in cortisol levels (CARi). Hierarchical multiple regression was employed to examine the influence of shift type on the sleep quality of the female nurses and the mediating effect of CARi. The results of this study indicate that shift type significantly influenced CARi (F = 19.66, p < 0.001) and that the regression coefficients of evening versus day shifts and night versus day shifts are both negative. Shift type also significantly influenced sleep quality (F = 15.13, p < 0.001), and the regression coefficients of evening versus day shifts and night versus day shifts are both positive. After controlling for the influence of shift type, CARi remained significantly correlated with sleep quality (ΔF = 5.17, p = 0.025). The results show that female evening-shift or night-shift nurses display significantly lower CARi and experience significantly poorer sleep quality than day-shift nurses. A greater CARi in the female shift nurses represents better sleep quality. Furthermore, the results prove that CARi is a mediating variable influencing the sleep quality of female shiftwork nurses.     

Elevated cortisol awakening response associated with early life stress and impaired executive function in healthy adult males

Experiencing early life stress (ELS) and subsequent dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis may play a role in the aetiology of mental health disorders. However, the exact mechanisms linking HPA-axis dysregulation with the development of psychopathology have not been fully delineated. Progress in this area is hampered by the complex and often conflicting associations found between markers of HPA-axis function and risk factors for mental health disorders such as impaired executive function (EF) and ELS. This study investigated the association of the cortisol awakening response (CAR) with ELS and EF in a healthy adult male population (n = 109, aged 21–63). As previous inconsistencies in CAR and ELS association studies may be the result of not considering ELS-related factors such as cumulative exposure, type of stressor and developmental timing of ELS, these were also investigated. The main findings were that the CAR was significantly elevated in individuals reporting ELS compared to those reporting no ELS (p = 0.007) and that an elevated CAR predicted poorer problem solving/planning (p = 0.046). Cumulative exposure, type of stressor and developmental timing of ELS were also found to impact significantly on the CAR. These results suggest that ELS is associated with chronic changes in HPA-axis function and that these changes may be associated with impairments in problem solving/planning. Future work should investigate further the neurobiological mechanisms linking ELS, the CAR and EF and their role in conferring risk for the development of mental health disorders.     

Combined effect of oxidative stress-related gene polymorphisms on atherosclerosis

It is well known that oxidative stress plays critical roles in the pathogenesis of atherosclerosis. In this study, we enrolled 1746 type 2 diabetic subjects, determined 4 common genetic variants related to oxidative stress (glutamate-cysteine ligase modifier subunit (GCLM) C-588T, myeloperoxidase G-463A, human paraoxonase 1 Gln192Arg and NAD(P)H oxidase p22phox C242T polymorphisms), and measured carotid intima-media thickness (IMT) as a surrogate marker for atherosclerosis. GCLM C-588T polymorphism was associated with average IMT (AveIMT) (r = 0.090, p = 0.0008), but the association between the other 3 polymorphisms and AveIMT did not reach the statistical significance. However, AveIMT was significantly greater as the total number of 4 concomitant “pro-oxidant alleles” in each subject was increased (r = 0.108, p < 0.0001). Furthermore, the number of “pro-oxidant alleles” was a risk factor for a high AveIMT independently of conventional risk factors (p = 0.0003). In conclusion, accumulation of oxidative stress-associated alleles was associated with carotid atherosclerosis in type 2 diabetic patients.     

Urinary free cortisone, but not cortisol, is associated with urine volume in severe obesity

Background

High urine volume enhances urinary free cortisol (UFF) and cortisone (UFE) excretion rates in normal-weight adults and children. Renal excretion rates of glucocorticoids (GC) and their metabolites are frequently altered in obesity. The aim of the present study was to investigate whether UFF and UFE excretion is also affected by urine volume in severely obese subjects.

Experimental

In 24-h urine samples of 59 extremely obese subjects (mean BMI 45.3 ± 8.9 kg/m²) and 20 healthy lean subjects (BMI 22.1 ± 1.8 kg/m²), UFF and UFE, tetrahydrocortisol (THF), 5α-tetrahydrocortisol (5α-THF), and tetrahydrocortisone (THE) were quantified by RIA. The sum of THF, 5α-THF, and THE (GC3), the three major GC metabolites, reflects daily cortisol secretion. 11β-Hydroxysteroid dehydrogenase type 2 (11β-HSD2) activity was assessed by the ratio UFE/UFF. Daily GC excretion rates were corrected for urine creatinine and adjusted for gender and body weight.

Results

In extremely obese subjects, urine volume was significantly associated with creatinine-corrected UFE and 11β-HSD2 activity after adjustment for gender and BMI (r = 0.47, p = 0.0002 and r = 0.31, p = 0.02, respectively). However, urine volume was not associated with creatinine-corrected UFF and GC3 (p = 0.4 and p = 0.6, respectively). In lean controls, urine volume was significantly associated with creatinine-corrected UFE and UFF (r = 0.58, p = 0.01 and r = 0.55, p = 0.02, respectively), whereas urine volume was not associated with 11β-HSD2 activity after appropriate adjustment (p = 0.3).

Conclusions

In severe obesity, in contrast to normal weight, renal excretion of UFE, but not of UFF is affected by fluid intake. This discrepancy may be due to the increased renal 11β-HSD2 activity in obesity.     

Hormones,behavior, and social network analysis: Exploring associations between cortisol,testosterone, and network structure

We used a new interdisciplinary paradigm of social network analysis (SNA) to investigate associations between hormones and social network structures. We examine these biobehavioral processes and test hypotheses about how hormones are associated with social network structures using exponential random graph modeling (ERGM) in a cohort of first-year students (n = 74; 93% female; M age = 27 years) from a highly competitive, accelerated nursing program. Participants completed friendship nominations and as a group simultaneously donated saliva (later assayed for cortisol and testosterone). ERGM analyses revealed that salivary cortisol levels were inversely associated with the number of outgoing ties (i.e., network activity). By contrast, testosterone was not related to friendship network structure. Integration of SNA and salivary bioscience creates a novel approach to understanding hormone–behavior relationships within the context of human social ecologies.     

High self-perceived stress and many stressors, but normal diurnal cortisol rhythm, in adults with ADHD (attention-deficit/hyperactivity disorder)

Attention-deficit/hyperactivity disorder (ADHD) in adults is associated with significant impairment in many life activities and may thus increase the risk of chronic stress in everyday life. We compared adults with a DSM-IV ADHD diagnosis (n = 28) with healthy controls (n = 28) regarding subjective stress and amounts of stressors in everyday life, diurnal salivary cortisol in the everyday environment and salivary cortisol before and after cognitive stress in a laboratory setting. The association between cortisol concentrations and impulsivity was also investigated. Consistent with assumptions, individuals with ADHD reported significantly more self-perceived stress than controls, and subjective stress correlated with the amount of stressors in everyday life. The two groups were comparable with respect to overall diurnal cortisol levels and rhythm, as well as in pre- and post-stress cortisol concentrations. Post-stress cortisol (but not baseline cortisol) concentration was positively correlated with impulsivity. The group with high post-stress cortisol also reported more symptoms of depression and anxiety, as well as self-perceived stress and stressors in every-day life. The diagnosis of ADHD significantly increased the risk of belonging to the group with high post-stress cortisol levels. The results in this study warrant a focus not only on the primary diagnosis of ADHD, but also calls for a broader assessment of stressors and subjective stress in everyday life, as well as support comprising stress management and coping skills.     

An in vivo microdialysis coupled with liquid chromatography/tandem mass spectrometry study of cortisol metabolism in monkey adipose tissue

It is postulated that elevated tissue concentrations of cortisol may be associated with the development of metabolic syndrome, obesity, and type 2 diabetes. The 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme regenerates cortisol from inactive cortisone in tissues such as liver and adipose. To better understand the pivotal role of 11β-HSD1 in disease development, an in vivo microdialysis assay coupled with liquid chromatography/tandem mass spectrometry (LC/MS/MS) analysis using stable isotope-labeled (SIL) cortisone as a substrate was developed. This assay overcomes the limitations of existing methodologies that suffer from radioactivity exposure and analytical assay sensitivity and specificity concerns. Analyte extraction efficiencies (E_d) were evaluated by retrodialysis. The conversion of SIL-cortisone to SIL-cortisol in rhesus monkey adipose tissue was studied. Solutions containing 100, 500, and 1000 ng/mL SIL-cortisone were locally delivered through an implanted 30-mm microdialysis probe in adipose tissue. At the delivery rate of 1.0 and 0.5 μL/min, E_d values for SIL-cortisone were between 58.7 ± 5.6% (n = 4) and 72.7 ± 1.3% (n = 4), whereas at 0.3 μL/min E_d reached nearly 100%. The presence of 11β-HSD1 activities in adipose tissue was demonstrated by production of SIL-cortisol during SIL-cortisone infusion. This methodology could be applied to cortisol metabolism studies in tissues of other mammalian species.     

Beyond physiological hypoarousal: The role of life stress and callous-unemotional traits in incarcerated adolescent males

The development of antisocial behavior in youth has been examined with neurobiological theories that suggest that adolescents who are less responsive to their environments are less likely to develop empathy in the absence of extant physiological arousal. However, little attention is paid to these individuals' social context. Individuals with adverse early experiences can also exhibit attenuated physiological arousal. The current investigation examines whether psychopathic symptoms or life stress exposure is associated with cortisol and its diurnal rhythm within 50 incarcerated adolescent boys (14–18 years old). Ten saliva cortisol samples were collected 1–2 weeks after admission to a maximum-security juvenile facility. Hierarchical Linear Modeling distinguished waking cortisol levels, the awakening response (CAR) and the diurnal rhythm. Multiple interviews and self-report measures of CU traits and stressor exposure were collected. Boys with higher levels of CU traits or greater life stress exposure had flat diurnal rhythms and a steeper awakening response in analyses with lifetime stress exposure specifically. Nonetheless, boys who were elevated on both CU traits and prior stress exposure had steeper diurnal rhythms. These results extend neurobiological theories of cortisol and illustrate that boys with the combination of severe stress with CU traits have a unique physiological profile.