Hair as a retrospective calendar of cortisol production-Increased cortisol incorporation into hair in the third trimester of pregnancy

Hair has long been used in toxicology, forensic science, doping control and other fields as a biological specimen for the detection of environmental agents, drugs, or toxins. Most recent evidence suggests that also hormones are incorporated and trapped inside the growing hair. This has led to the hypothesis that cortisol measurement of distinct hair segments could provide a retrospective calendar of cortisol production for the individual. In this first proof-of-concept study in humans, we analyzed cortisol in hair donated by mothers with a neonate child (n-Mothers; N=103), mothers with toddlers 3-9 months of age (t-Mothers; N=19), and control women (N=20). We cut hair strands from each women into at least three 3-cm segments, which, based on an average hair growth rate of 1cm per month, would represent hair grown over the past three, six, and nine months, respectively. Since in the third trimester of pregnancy there is a well-documented increased production of cortisol, we expected to see elevated levels of cortisol in the most proximal hair segment of women who had just given birth to a child (n-Mothers) compared with the control women. Likewise, we expected to see elevated levels in the second, third, or fourth segment of mothers of 3-month olds, 6-months olds, and 9-months olds, respectively. These hair segments, cut at 4-12 cm from the scalp, would represent hair grown throughout the third trimester of pregnancy. Results showed that there was a strong monotonic decline in cortisol concentration from the segment closest to the scalp to the most distal hair segment (p<0.0001). Cortisol levels decreased by 30-40% from one segment to the next for the most recent four hair segments. Segments from hair older than one year had similarly, low levels of cortisol. Comparisons of cortisol levels in hair between n-Mothers and control women yielded the expected results: cortisol levels in the first 3-cm hair segment (i.e., closest to the scalp) of n-Mothers were two-fold higher than in controls (p<0.0001), probably reflecting increased cortisol levels throughout the third trimester of pregnancy. No differences in cortisol content were apparent for the second or third 3-cm segments in n-Mothers (p>0.2). When hair from mothers with 6-9 months old toddlers was analyzed, the hair segment representing the third trimester period contained the same amount of cortisol as the hair grown more recently in mothers with 3-4 months old toddlers only. Age of the women, hair curvature, hair color, and frequency of hair washes per week were unrelated to cortisol levels. We conclude that cortisol measured in human hair can be a valid reflection of increased cortisol production for a period of up to six months. Due to a rapid decline of cortisol levels in human adult hair, a retrospective calendar of cortisol exposure may be limited to the past six months.     

Increased cortisol concentrations in hair of severely traumatized Ugandan individuals with PTSD

Previous research has mostly suggested general hypocortisolism in posttraumatic stress disorder (PTSD). However, PTSD is a complex disorder and opposite neuroendocrinological changes have also been reported. Amongst other things, heterogeneous results might be related to differences in sample characteristics as well as methodological factors associated with the assessment of cortisol. The current study used the novel method of hair cortisol analysis to examine cumulative long-term cortisol secretion in a severely traumatized PTSD sample. Hair samples of 10 traumatized individuals with PTSD and 17 traumatized controls without PTSD from a civil war area of Northern Uganda were analyzed. Results revealed that hair samples of PTSD participants contained higher cortisol levels than those of traumatized controls (p<.05). Furthermore, a positive association between hair cortisol levels and the number of lifetime traumatic events was found (p<.05). The current hair cortisol findings suggest that PTSD in severely traumatized individuals who continue to live under stressful conditions might be associated with general hypercortisolism. Future research examining participants after traumatic events at different follow-up periods is needed to determine the specific influence of time interval since traumatization.     

Decreased hair cortisol concentrations in generalised anxiety disorder

Previous research examining hypothalamic-pituitary-adrenal (HPA) axis activity in generalised anxiety disorder (GAD) has suggested a general hypercortisolism. These studies have mostly relied on salivary, plasma or urinary assessments, reflecting cortisol secretion over short time periods. The current study utilised the novel method of cortisol assessment in hair to obtain a retrospective index of cortisol secretion over a prolonged period of time. Hair cortisol levels were determined in 15 GAD patients and in 15 age- and gender-matched controls. In addition, participants collected six saliva samples (on awakening, +30 min, 12:00, 16:00, 20:00 h and at bedtime) on two consecutive weekdays for the assessment of the diurnal cortisol profile. Results revealed significantly lower (50-60%) cortisol levels in the first and second 3-cm hair segments of GAD patients compared to those of controls. No significant between-group differences were seen in diurnal cortisol profiles. The hair cortisol findings tentatively suggest that under naturalistic conditions GAD is associated with hypocortisolism. If corroborated by future research, this demonstrates the important qualities of cortisol measurement in hair as an ecologically valid, retrospective index of long-term cortisol secretion and as a marker for psychiatric disorders associated with hypo- or hypercortisolism.     

Intraindividual stability of hair cortisol concentrations

The analysis of cortisol in human hair constitutes a promising method for the retrospective assessment of cumulative cortisol secretion over extended periods of time. An implicit assumption underlying the use of this method is that in the absence of major life changes hair cortisol concentrations show a high level of intraindividual stability, i.e. single hair cortisol assessments exhibit considerable trait-specificity and are only to a smaller extent influenced by state-dependent factors. Here, we present data from two independent studies examining patterns of intraindividual stability in hair cortisol levels. In study I, 45 participants were examined at two sampling points carried out one year apart from each other. In study II, 64 individuals provided data at three sampling points which occurred at two-month intervals. In both studies, at each time point hair was sampled and relevant psychosocial and hair-related variables were assessed. Results of both studies consistently revealed strong test-retest associations for repeated hair cortisol measurements ('r's between 0.68 and 0.79, 'p's <0.0001). Findings of structural equation modelling applied to data of study II showed that single hair cortisol assessments comprise a strong trait component, explaining between 59 and 82% of variance, and are only to a lesser extent influenced by state-related factors. Only inconsistent evidence for covariation of changes in hair cortisol concentrations and simultaneous changes in perceived stress or other relevant variables was seen across the two studies. The current findings suggest a considerable degree of intraindividual stability in hair cortisol levels which highlights the utility of this method for obtaining trait estimates of long-term cortisol secretion in psychoneuroendocrinological research.     

Physiological and behavioral adaptation to relocation stress in differentially reared rhesus monkeys: hair cortisol as a biomarker for anxiety-related responses

Increased hair cortisol concentrations have been associated with stress exposure in both human and nonhuman primates, and hair cortisol is now gaining attention as a biomarker for stress-related health problems. The present study examined the behavioral and physiological reactions of rhesus monkey (Macaca mulatta) infants reared in three different rearing environments to the major stressor of relocation. Infant monkeys (n=61) were studied from birth through 2 years of age. For the first 8 months of life, infants were either with their mothers and peers (MPR, n=21) or reared in a nursery using either peer-rearing (PR, n=20) or surrogate-peer-rearing (SPR, n=20). At approximately 8 months of age, infants were removed from their rearing group, simultaneously placed into a large social environment consisting of infants from all three rearing conditions, and observed for the next 16 months. Behavior was recorded twice per week from 1 to 24 months, and composite anxiety scores were calculated for each monkey. Monkeys were initially shaved at the nape of the neck on day 14 to remove any prenatal effects on hair cortisol deposition. Hair samples were then collected by re-shaving at 6, 12, 18 and 24 months and analyzed for cortisol content. MPR monkeys were the least affected by the stressor, showing smaller increases in anxious behavior than the other groups and more rapid physiological adaptation as assessed using hair cortisol. PR monkeys showed heightened and prolonged anxious behavior, had the highest cortisol levels prior to relocation, and their cortisol levels did not decline until more than a year later. SPR monkeys exhibited more rapid behavioral adaptation than PR monkeys, showing heightened but not prolonged anxious behavior. However, the SPR group showed a marked increase in cortisol in response to the relocation, and like the PR group, their physiological adaptation was slower than that of the MPR group as indicated by elevated cortisol levels at 18 months. By 24 months of age (16 months after relocation), all rearing groups were indistinguishable from one another physiologically and behaviorally. Spearman rank correlation revealed that hair cortisol taken at month 6 was not correlated with composite anxiety scores from months 6 to 8 (just before the relocation), but was positively correlated with composite anxiety scores between months 8 and 12 (immediately after relocation) for PR infants only (r(s)=0.75, p<0.001). Month 6-hair cortisol tended to positively correlate with composite anxiety scores for the following 6 months (months 12-18) for PR monkeys only (r(s)=0.47, p=0.037), which exhibited more anxious behavior than MPR and SPR infants during this period (ANOVA: F((2,60))=14.761, p<0.001) This is the first study to show that elevated hair cortisol early in life is a biomarker for the later development of anxious behavior in response to a major life stressor, particularly for infant monkeys exposed to early life adversity in the form of peer-rearing.     

Hair cortisol,stress exposure,and mental health in humans: A systematic review

The deleterious effects of chronic stress on health and its contribution to the development of mental illness attract broad attention worldwide. An important development in the last few years has been the employment of hair cortisol analysis with its unique possibility to assess the long-term systematic levels of cortisol retrospectively. This review makes a first attempt to systematically synthesize the body of published research on hair cortisol, chronic stress, and mental health. The results of hair cortisol studies are contrasted and integrated with literature on acutely circulating cortisol as measured in bodily fluids, thereby combining cortisol baseline concentration and cortisol reactivity in an attempt to understand the cortisol dynamics in the development and/or maintenance of mental illnesses. The studies on hair cortisol and chronic stress show increased hair cortisol levels in a wide range of contexts/situations (e.g. endurance athletes, shift work, unemployment, chronic pain, stress in neonates, major life events). With respect to mental illnesses, the results differed between diagnoses. In major depression, the hair cortisol concentrations appear to be increased, whereas for bipolar disorder, cortisol concentrations were only increased in patients with a late age-of-onset. In patients with anxiety (generalized anxiety disorder, panic disorder), hair cortisol levels were reported to be decreased. The same holds true for patients with posttraumatic stress disorder, in whom – after an initial increase in cortisol release – the cortisol output decreases below baseline.     

The relationship between cortisol,stress and psychiatric illness: New insights using hair analysis

BackgroundStress is an established important contributor to the development of mental illness and stress related disorders. The biology implicated in the homeostasis of pathological stress mechanisms is not fully established. One of the difficulties with current techniques is the limitation in capturing chronic levels of cortisol as an expression of stress levels in humans. Hair samples can be used to evaluate cortisol levels averaged over relatively long periods of time, therefore providing a more valid measure of chronic levels of this hormone. A highly replicable technique to measure long-term cortisol could prove pivotal in improving our understanding of the role of stress in psychiatric disorders.MethodsThis review synthesises all the published studies relating hair cortisol concentration (HCC) to stress and to psychiatric disorders. It describes and summarises their findings with the aim of providing a summary picture of the current state of this line of research.ResultsThe strongest finding to date is the replicable increases in hair cortisol associated with stressful life events. Findings in psychiatric disorders are more sparse and inconsistent. There is some support for the presence of raised HCC in major depressive disorders, and for lowered HCC in posttraumatic stress disorder, suggesting chronic hypercortisolaemia and hypocortisolaemia respectively.ConclusionsHCC is a promising methodology to study chronic cortisol levels with the potential to help characterise psychiatric and stress related disorders. The combination of chronic and acute cortisol measurements has the potential for more accurately determining different aspects of the stress response, and ultimately for the development of a biological marker to aid diagnosis and response to treatment.     

The long-term association of adverse childhood experiences with C-reactive protein and hair cortisol: Cumulative risk versus dimensions of adversity

BackgroundExposure to adverse childhood experiences (ACEs) may lead to stress-induced upregulation of inflammatory and neuroendocrine processes. However, it remains unclear whether such effects persist into later life, and which dimensions of ACEs might have the strongest impact on these biological mechanisms. Therefore, this study investigated the effects of ACEs on C-reactive protein (CRP) and hair cortisol in a large sample of older adults, distinguishing between cumulative exposure and dimensions of ACEs.MethodsWe utilised data from the English Longitudinal Study of Ageing. ACEs were assessed through retrospective reports at wave 3(2006/07). CRP (N = 4198) was measured at waves 4(2008/09) and 6(2012/13), and hair cortisol (N = 3357) at wave 6. The effects of ACEs cumulative exposure were examined using linear and ordinal logistic regression analysis. ACEs dimensions (i.e. threat, household dysfunction, low parental bonding, and loss of an attachment figure) were identified using explorative and confirmatory factor analysis with cross-validation. All analyses were adjusted for relevant confounders.ResultsParticipants with three or more ACEs had higher CRP levels at wave 4 and an elevated risk of high CRP concentrations across waves 4 and 6 compared with those who did not experience any ACEs. The four ACEs dimensions were all positively associated with both CRP outcomes and had similar effect sizes. In contrast, neither the cumulative score nor the dimensions of ACEs were significantly related to hair cortisol. However, there was a positive, yet small, interaction effect between ACEs and age on hair cortisol.ConclusionOlder adults who retrospectively reported three or more ACEs had chronically elevated CRP levels and exhibited a slightly steeper increase in hair cortisol with age. Different dimensions of ACEs had similar associations with the biomarkers.     

Hair cortisol as a biological marker of chronic stress: current status, future directions and unanswered questions

The detrimental effects of stress on human health are being increasingly recognized. There is a critical need for the establishment of a biomarker that accurately measures its intensity and course over time. Such a biomarker would allow monitoring of stress, increase understanding of its pathophysiology and may help identify appropriate and successful management strategies. Whereas saliva and urine cortisol capture real-time levels, hair cortisol analysis presents a complementary means of monitoring stress, capturing systemic cortisol exposure over longer periods of time. This novel approach for cortisol quantification is being increasingly used to identify the effects of stress in a variety of pathological situations, from chronic pain to acute myocardial infarctions. Because of its ability to provide a long-term, month-by-month measure of systemic cortisol exposure, hair cortisol analysis is becoming a useful tool, capable of answering clinical questions that could previously not be answered by other tests. In this paper we review the development, current status, limitations and outstanding questions regarding the use of hair cortisol as a biomarker of chronic stress.     

Analysis of cortisol in hair - State of the art and future directions

Changes to long-term secretion of the glucocorticoid cortisol are considered to play a crucial role in mediating the link between chronic stress and the development of numerous immune system related diseases. However, obtaining valid assessments of long-term cortisol levels is difficult due to limitations of previous measurement strategies in blood, saliva or urine. This review discusses evidence on a recent methodological development assumed to provide a considerable advancement in this respect: the analysis of cortisol in hair. Being incorporated into the growing hair, hair cortisol concentrations (HCC) are assumed to provide a retrospective reflection of integrated cortisol secretion over periods of several months. Over the past years, supportive evidence has accumulated regarding several fundamental characteristics of HCC, including its validity as an index of long-term systemic cortisol levels, its reliability across repeated assessments and its relative robustness to a range of potential confounding influences. Based on this groundwork, research has now also commenced to utilise HCC for answering more specific questions regarding the role of long-term cortisol secretion in different stress and health-related conditions. The possibility of extending hair analysis to also capture long-term secretion of other steroid hormones (e.g., androgens or estrogens) provides a further intriguing prospect for future research. Given its unique characteristics, the use of hair analysis holds great promise to significantly enhance current understanding on the role of steroid hormones in psychoimmunological research.     

Developmental patterns of hair cortisol in male and female nonhuman primates: Lower hair cortisol levels in vervet males emerge at puberty

Studies have yielded inconsistent results with regard to effects of age and sex on short-term markers of hypothalamic pituitary adrenal (HPA) activity. Hair cortisol provides a retrospective proxy measure of the cumulative activity of the HPA axis over the preceding 3- to 4-month period. In order to describe potential developmental trends in this biomarker, we assessed hair cortisol levels between 1 and 12 years of age in a cross-sectional study of 350 vervets (222 females and 128 males). Monkeys were grouped according to age as 1 (young juvenile), 2 (juvenile), 3 (early adolescent), 4 (late adolescent-young adult), and 5-12 (adult) years of age such that fully mature animals were included in the 5-12 year old age group. We observed that hair cortisol level was higher among the younger monkeys and declined with age (p<.001). More importantly the effect of age significantly interacted with sex (p=.02), such that hair cortisol was consistently lower in males than females beginning at age 3 (p<.05 or better). The developmental decline began one year earlier in females than males suggesting an influence of the earlier maturational processes typical in both human and nonhuman primates. The advantage of lower cortisol levels in the males may be related to social group patterns of male emigration during adolescence in many nonhuman primate species.     

Heritability and genetic correlation of hair cortisol in vervet monkeys in low and higher stress environments

Chronic activation of the hypothalamic-pituitary adrenal (HPA) system is a risk factor for a variety of physical and mental disorders, and yet the complexity of the system has made it difficult to define the role of genetic and environmental factors in producing long-term individual differences in HPA activity. Cortisol levels in hair have been suggested as a marker of total HPA activation over a period of several months. This study takes advantage of a pedigreed nonhuman primate colony to investigate genetic and environmental influences on hair cortisol levels before and after an environmental change. A sample of 226 adult female vervet monkeys (age 3-18) living in multigenerational, matrilineal social groups at the Vervet Research Colony were sampled in a stable low stress baseline environment and 6 months after the entire colony was moved to a new facility with more frequent handling and group disturbances (higher stress environment). Variance components analysis using the extended colony pedigree was applied to determine heritability of hair cortisol levels in the two environments. Bivariate genetic correlation assessed degree of overlap in genes influencing hair cortisol levels in the low and higher stress environments. The results showed that levels of cortisol in hair of female vervets increased significantly from the baseline to the post-move environment. Hair cortisol levels were heritable in both environments (h(2)=0.31), and there was a high genetic correlation across environments (rhoG=0.79), indicating substantial overlap in the genes affecting HPA activity in low and higher stress environments. This is the first study to demonstrate that the level of cortisol in hair is a heritable trait. It shows the utility of hair cortisol as a marker for HPA activation, and a useful tool for identifying genetic influences on long term individual differences in HPA activity. The results provide support for an additive model of the effects of genes and environment on this measure of long term HPA activity.     

Relationship between effort–reward imbalance and hair cortisol concentration in female kindergarten teachers

Objective

The present study aims to investigate the relationship between effort–reward imbalance and hair cortisol concentration among teachers to examine whether hair cortisol can be a biomarker of chronic work stress.

Methods

Hair samples were collected from 39 female teachers from three kindergartens. Cortisol was extracted from the hair samples with methanol, and cortisol concentrations were measured with high performance liquid chromatography–tandem mass spectrometry. Work stress was measured using the effort–reward imbalance scale.

Results

The ratio of effort to reward showed significantly positive association with hair cortisol concentration.

Conclusion

The cortisol concentration in the system increases with the effort–reward imbalance. Measurement of hair cortisol can become a useful biomarker of chronic work stress.     

Cognitive behavioral stress management effects on injury and illness among competitive athletes: A Randomized Clinical trial

Cognitive behavioral stress management (CBSM) has previously been found to reduce fatigue, depression, and cortisol response to heavy exercise training among competitive collegiate athletes and to speed physical and psychological recovery from surgery (1,2). Our study assessed the efficacy of a CBSM program to reduce the frequency of injury and illness among collegiate athletes in a randomized, single-blind, controlled clinical trial. Following assessment of baseline medical history, mood state, stress, cortisol, sleep, alcohol use, and exercise training, collegiate rowers were stratified by gender and competitive level and randomly assigned to either a control group or a CBSM group. Exercise training information and psychosocial assessments were repeated immediately following the intervention period, and health care providers who were blinded to participant assignment recorded the frequency of medical visits and the number of days injured or ill until the end of the season. Athletes randomly assigned to a CBSM group experienced significant reductions in the number of illness and injury days as compared to control group athletes. CBSM participants also had half the number of health service visits as did controls. The data suggest that a time-limited CBSM intervention designed specifically for an athlete population may be an effective prophylactic treatment to reduce the incidence of injury and illness among competitive collegiate athletes.     

Association between hair cortisol concentration and perceived stress in female methamphetamine addicts

ObjectiveThe present study aims to explore whether hair cortisol concentration is associated with explicit stress or implicit stress in female methamphetamine addicts.MethodsHair samples were collected from 51 female methamphetamine addicts from inpatient addiction treatment programs. Perceived stress was assessed by both explicit and implicit measures through the Perceived Stress Scale (PSS) and the Implicit Association Test (IAT), respectively.ResultsThe positive relationship between hair cortisol concentration with D-scores of the IAT reached statistically significant difference. A marginal correlation between hair cortisol concentration and scores of the PSS was observed. Additionally, linear regression analysis indicated that D-scores of the IAT are strongly predictive of hair cortisol concentration.ConclusionHair cortisol concentration is strongly related to implicit stress but only weakly related with explicit stress.     

Carnitine in muscle, serum, and urine of nonprofessional athletes: effects of physical exercise, training, and L-carnitine administration

Efficient utilization of fatty acids to sustain prolonged physical efforts is thought to be dependent on the carnitine shuttle of muscle. A study has been carried out in 24 athletes (13 long-distance runners and 11 sprinters). These subjects received placebo or L-carnitine (1 g/orally b.i.d.) during a 6-month period of training. In endurance athletes, training induced lowering of total and free muscle carnitine. Increase of esterified muscle carnitine was also observed. Post-exertional overflow of acetylcarnitine and long-chain acylcarnitine, as well as reduction of the free fraction was also noticed in the blood. Fasting plasma carnitine levels, however, were not affected in carnitine-treated athletes at rest. These changes were likely related with the significantly increased urinary excretion of esterified and total carnitine which occurred after physical exercise. In the sprinters only, a decrease in free and total carnitine of muscle was detected after training. Both these potentially unfavorable effects were prevented by oral administration of L-carnitine. Our data suggest that training in endurance athletes, and to a lesser extent, in sprinters, is associated with a decrease in free and total carnitine of muscle, due to an increased overflow of short-chain carnitine esters in urine.     

Intimate partner violence is associated with increased maternal hair cortisol in mother–child dyads

BackgroundThe chronic consequences of intimate partner violence (IPV) on HPA activation are a topic of debate. The current study investigated hair cortisol concentrations in female victims of IPV and their children.MethodsA total of 52 mother–child dyads were divided into two groups depending on exposure to IPV: IPV group (n = 27 dyads) and control group (n = 25 dyads). Hair cortisol concentration was measured in 1-cm-long hair strands, representing 30 days of exposure before assessment. PTSD and depression symptoms were assessed in the mother and child.ResultsWomen reporting IPV presented with higher hair cortisol levels, depression and PTSD symptoms severity in comparison to control women. Children who witnessed IPV reported more severe PTSD symptoms, but depressive symptoms and hair cortisol were not statistically different than those in control children. Correlation analyses revealed a positive association between the number of injury events and the level of hair cortisol in children. No associations between the hair cortisol levels in mothers and those in their children were found.ConclusionHigher hair cortisol levels detected in women exposed to IPV reflected long-lasting changes in HPA axis functioning associated with chronic stress exposure. Children whose parents recurrently engage in violent conflicts with intimate partners may often feel threatened and consequently reporting more PTSD-related symptoms. Given that experiencing and witnessing violence during childhood and adolescence are predictive of intimate partner violence in adulthood, the need of early interventions is crucial.     

Variability of antiepileptic medication taking behaviour in sudden unexplained death in epilepsy: hair analysis at autopsy

BACKGROUND: Variable compliance with antiepileptic drugs (AEDs) is a potentially preventable cause of sudden unexplained death in epilepsy (SUDEP). Hair AED concentrations provide a retrospective insight into AED intake variability. METHODS: We compared hair AED concentration variability in patients with SUDEP (n = 16), non-SUDEP epilepsy related deaths (n = 9), epilepsy outpatients (n = 31), and epilepsy inpatients (n = 38). AED concentrations were measured in 1 cm hair segments using high performance liquid chromatography. Individual patient hair AED concentration profiles were corrected for "washout" using linear regression analysis. The coefficient of variation (CV) of the corrected mean hair AED concentration provided an index of variability of an individual's AED taking behaviour. Hair sample numbers varied between subjects, and so weighted regression estimates of the CV were derived for each group. RESULTS: The CV regression estimates for each group were: SUDEP 20.5% (standard error 1.9), non-SUDEP 15.0% (3.9), outpatients 9.6% (1.4), and inpatients 6.2% (2.7). The SUDEP group therefore showed greater hair AED concentration variability than either the outpatient or the inpatient groups (p<0.0001). CONCLUSION: Observed variability of hair AED concentrations, reflecting variable AED ingestion over time, is greater in patients dying from SUDEP than in either epilepsy outpatients or inpatients. SUDEP, at least in a proportion of cases, appears preventable.     

Repeating patterns of sleep restriction and recovery: Do we get used to it?

Despite its prevalence in modern society, little is known about the long-term impact of restricting sleep during the week and ‘catching up’ on weekends. This common sleep pattern was experimentally modeled with three weeks of 5 nights of sleep restricted to 4 h followed by two nights of 8-h recovery sleep. In an intra-individual design, 14 healthy adults completed both the sleep restriction and an 8-h control condition, and the subjective impact and the effects on physiological markers of stress (cortisol, the inflammatory marker IL-6, glucocorticoid receptor sensitivity) were assessed. Sleep restriction was not perceived to be subjectively stressful and some degree of resilience or resistance to the effects of sleep restriction was observed in subjective domains. In contrast, physiological stress response systems remain activated with repeated exposures to sleep restriction and limited recovery opportunity. Morning IL-6 expression in monocytes was significantly increased during week 2 and 3 of sleep restriction, and remained increased after recovery sleep in week 2 (p < 0.05) and week 3 (p < 0.09). Serum cortisol showed a significantly dysregulated 24 h-rhythm during weeks 1, 2, and 3 of sleep restriction, with elevated morning cortisol, and decreased cortisol in the second half of the night. Glucocorticoid sensitivity of monocytes was increased, rather than decreased, during the sleep restriction and sleep recovery portion of each week. These results suggest a disrupted interplay between the hypothalamic-pituitary-adrenal and inflammatory systems in the context of repeated exposure to sleep restriction and recovery. The observed dissociation between subjective and physiological responses may help explain why many individuals continue with the behavior pattern of restricting and recovering sleep over long time periods, despite a cumulative deleterious physiological effect.     

Cortisol awakening response in abstinent alcohol-dependent patients as a marker of HPA-axis dysfunction

Hypothalamo-pituitary-adrenocorticoid (HPA)-axis reactivity to psychosocial or pharmacological stimulants is diminished in alcohol-dependent patients during early abstinence but recovers after several months of abstention. In order to assess the physiological reactivity in the morning we used the cortisol awakening response (CAR) in saliva to compare 24 early abstainers (mean 21.9+/-7.6, range 10-36 days) with 12 alcohol-dependent patients with longer abstention periods (mean 116.8+/-45.7, range 59-230 days) and looked for an association with sleep, especially rapid eye movement (REM) sleep of the preceding night. Both groups did not differ with respect to age, duration of alcohol dependence, daily drinking dosage before detoxification, body mass index, depressivity, level of anxiety, daily cigarette consumption or sleep quality during the preceding 14 days. Sleep in the night before cortisol assessment did not differ with respect to total sleep time (412.4+/-35.9 vs. 407.0+/-38.7 min). Immediately upon awakening and 15, 30, 45 and 60 min later, specimens of salivary cortisol were collected. While starting from equal levels upon awakening longer abstaining patients with alcohol dependence showed a stronger CAR (ANOVA with repeated measurement, time x group effect: F=4.33, p<0.01) with distinctly higher cortisol levels 45 and 60 min after awakening (T=3.79, p<0.001 and T=3.06, p<0.005, respectively). Across both groups the time spent in REM-sleep only correlated with cortisol levels upon awakening (r=0.33, p<0.05). Our data indicate that CAR is a useful tool for investigating alterations in the HPA-axis regulation in abstaining alcohol-dependent patients.