Differences In Cortisol Responses Research Articles

1092 – Cortisol awakening response (CAR) and gender differences in adults with attention deficit hyperactivity disorder (ADHD)

Ahe adult patients with attention deficit hyperactivity disorder (ADHD) are characterized by an increased vulnerability to daily life stressors. Cortisol awakening response (CAR) can be used as an index of the adrenocortical activity that relates to chronic stress. Although gender differences in cortisol response have been explored in children with ADHD, there is a lack of gender studies in adults with this disorder. The aim of the present study is to evaluate possible gender differences in CAR in adults with ADHD. A total of 50 patients (22 female, age 37.00±8.62 years, and 28 male, age 33.86±9.57 years), with ADHD were recruited from the program for adults with ADHD in the Department of Psychiatry of the Hospital Universitari Vall d’Hebron. Patients fulfilled current DSM-IV diagnostic criteria for ADHD. Psychiatric and organic comorbid disorders were excluded and all the patients were naïve to psychostimulant treatment. Four salivary cortisol samples were collected at 0, 30, 45 and 60 minutes after awakening (work days). Mean increase in CAR was 10.39±8.68 nmols/l for men and 10.29±9.13 nmols/l for women. T-test comparisons showed no significant gender differences in CAR in adults with ADHD (t= 0.033, z=0.974). As reported in children, adults with ADHD show no differences in CAR. Albeit these results are still preliminary, they suggest some gender differences in CAR between adults with ADHD and cortisol response in general population.

Linking cortisol responsiveness and aggressive behaviour in gilthead seabream Sparus aurata: Indication of divergent coping styles

Farmed animals, including fish, often exhibit a pronounced individual variation in stress coping styles with proactive and reactive individuals differing in a variety of neuroendocrine and behavioural responses. In this study we disclosed that individual differences in cortisol responsiveness after a restraining test were predictive of aggressive behaviour in gilthead seabream Sparus aurata, one of the most important Mediterranean farmed fish. Seabream juveniles (n=24, initial weight: 49.3±7.3g) were exposed to a restraining test that consisted of keeping each fish in an emerged net for three minutes. Afterwards fish returned to their home tank and 30min after were rapidly caught and anaesthetised for blood sampling. Blood was collected from the caudal vein and analysed for cortisol (radioimmunoassay). After 3 months the same individuals were exposed to an aggression test: fish were allowed to interact with a naïve fish of similar size (max 10% weight difference) for 20min. Aggressive behaviour was determined as follows: latency to start chasing (time taken until the first chase; chase was defined as a sudden change in swimming direction and speed as a response to an approach by the opponent); number of chases; latency to fighting (time taken until the first fight; fight was defined when fish engaged in a circle movement around each other) and number of fights. Results showed that individuals exhibiting lower cortisol responsiveness after a restraining test were more aggressive (cortisol vs number of chases: rs=−0.479, p=0.021) In conclusion, seabream juveniles exhibited pronounced individual differences in cortisol responsiveness and aggression that are interrelated and likely to be distinctive traits of coping styles.

Fish age, instead of weight and size, as a determining factor for time course differences in cortisol response to stress

In many vertebrate species, including humans, the developmental stage directly influences an organism's reactivity to stress. For instance, fishes appear to exhibit “stress insensitive” periods early in development, which contributes to important alterations in stress responses. This phenomenon raises the important question of whether size or age influences fish stress responses, as there may be large discrepancies in size at any stage of ontogeny. We therefore posed the following question: what key role does the age and/or weight/length of fish play in contributing to different stress levels? To address this question, we conducted 2 simple experiments to compare the cortisol response to stress in the fish Rhamdia quelen. In the first experiment, we compared the cortisol response of fish of 2 different age groups (3 vs. 12months) with the same body size, whereas in the second experiment we compared 2 groups of the same age (3months) but with different body sizes. The results showed a similar stress response in fish of the same age but different size, but a large difference in the stress response in fish of the same size but different age. Both tests indicate that age is the determining factor for the functioning of the hypothalamo-pituitary-interrenal (HPI) axis, and is probably related to the stage of maturation. This study makes a significant contribution to our knowledge of the stress, behavior, and welfare of fish of different age classes, primarily with respect to the timing of measurements and the accurate determination of fish age, regardless of size.

Social familiarity modulates personality trait in a cichlid fish

Personality traits, such as exploration-avoidance, are expected to be adaptive in a given context (e.g. low-risk environment) but to be maladaptive in others (e.g. high-risk environment). Therefore, it is expected that personality traits are flexible and respond to environmental fluctuations, given that consistency across different contexts is maintained, so that the relative individual responses in relation to others remains the same (i.e. although the magnitude of the response varies the differences between high and low responders are kept). Here, we tested the response of male cichlid fish (Oreochromis mossambicus) to a novel object (NO) in three different social contexts: (i) social isolation, (ii) in the presence of an unfamiliar conspecific, and (iii) in the presence of a familiar conspecific. Males in the familiar treatment exhibited more exploratory behaviour and less neophobia than males in either the unfamiliar or the social isolation treatments. However, there were no overall correlations in individual behaviour across the three treatments, suggesting a lack of consistency in exploration-avoidance as measured by the NO test in this species. Moreover, there were no differences in cortisol responsiveness to an acute stressor between the three treatments. Together, these results illustrate how behavioural traits usually taken as measures of personality may exhibit significant flexibility and lack the expected consistency across different social contexts.

Cortisol responses in children and adults with attention deficit hyperactivity disorder (ADHD): a possible marker of inhibition deficits

Attention deficit hyperactivity disorder (ADHD) is a heterogeneous disease whose neurobiological background is not completely understood. It has been proposed that deficits of the inhibitory function with an underactive behavioral inhibition system (BIS) may be in the core of ADHD. In this regard, this review summarizes all studies that examine the involvement of cortisol in ADHD. Differences in cortisol responses from different ADHD subtypes, hyperactive/impulsive, inattentive, and combined, are analyzed. In addition, we examine the role of comorbidities as confounding factors in the study of cortisol in ADHD, including comorbid disruptive behavioral disorder (DBD), as well as anxiety and depressive disorders. Because ADHD is a neurodevelopmental condition and approximately half of the children enter adulthood with the disorder, we review cortisol studies in adults and children separately. Two diverse patterns of cortisol have been reported both in children and adults with ADHD. Blunted cortisol responses to stress are associated with comorbid DBD, whereas high cortisol responses are associated to comorbid anxiety disorders. Nevertheless, the inhibitory deficits in ADHD do not appear to be related directly to cortisol deficits in either children or adults. This review increases our understanding of the heterogeneity of ADHD and could help in determining new strategies for the treatment of these patients. Future studies including gender and a more systematic methodology to study the cortisol response are needed.

Naltrexone effects on cortisol secretion in women and men in relation to a family history of alcoholism: Studies from the Oklahoma Family Health Patterns Project

Naltrexone evokes a cortisol response through its blockade of central opioid receptors on the hypothalamic-pituitary-adrenocortical axis (HPA). The magnitude of this cortisol response may be useful as a probe for central opioid activity in different groups of subjects. Accordingly, the present study examined the effect of opioid blockade on the HPA in 70 women and 58 men with (N=41) and without (N=87) a family history of alcoholism, using a randomized, placebo-controlled, double blind administration of oral naltrexone (50mg). Saliva cortisol was sampled at baseline prior to placebo or naltrexone and again every 30 min over the next 180 min. Women had significantly larger cortisol responses to naltrexone than did the men, F=6.88, p<0.0001. There were no significant differences in cortisol response between groups differing in family history of alcoholism, F=0.65, p>0.69. The present results confirm that women have much greater central opioid restraint on the HPA than men do and that this endogenous restraint is unmasked by opioid blockade. However the results provide no evidence of a differential central opioid tonus in persons with a family history of alcoholism at this dose of naltrexone. The cortisol response to naltrexone may be a useful probe for central opioid activity in women and to a lesser degree in men.

Sex differences in HPA axis activity in response to a meal

BackgroundSex may influence the relationship between HPA axis functioning and obesity. This has been suggested to be due to sex-specific differences in body composition, body fat distribution and psychological variables. Age and the use of oral contraceptives may also influence the relationship between HPA axis functioning and obesity. ObjectiveTo systematically investigate whether body composition, body fat distribution, psychological variables, age, or possible oral contraceptive use contribute to sex differences in HPA axis activity in response to a meal. MethodsSubjects were men (n=19) and women (n=19) between 18 and 51years old with BMI between 20.3 and 33.2kg/m2. HPA axis activity was measured by salivary free cortisol levels before consuming a meal, and at 45, 75 and 125min postprandial on four repeated test days. Anthropometric and body composition measurements were performed. Questionnaires were used to assess cognitive eating behavior and trait anxiety level. ResultsNo differences between the test days in postprandial cortisol responses appeared. Responses were significantly higher in men compared with women (p<.05). No significant correlations were found between cortisol concentrations and sex-specific body composition or body fat distribution. Psychological variables did not contribute to differences in cortisol responses after a meal between men and women. In women, baseline cortisol concentrations correlated inversely with age (p=.024). ConclusionHigher HPA axis activity following a meal in men vs. women remained irrespective of sex-specific differences in body composition, body fat distribution, psychological variables, or in age. In women baseline cortisol concentrations were age-dependent.

A Discordant Monozygotic Twin Design Shows Blunted Cortisol Reactivity Among Bullied Children

Childhood adverse experiences are known to engender persistent changes in stress-related systems and brain structures involved in mood, cognition, and behavior in animal models. Uncertainty remains about the causal effect of early stressful experiences on physiological response to stress in human beings, as the impact of these experiences has rarely been investigated while controlling for both genetic and shared environmental influences. We tested whether bullying victimization, a repeated adverse experience in childhood, influences cortisol responses to a psychosocial stress test (PST) using a discordant monozygotic (MZ) twin design. Thirty pairs (43.3% males) of 12-year-old MZ twins discordant for bullying victimization were identified in the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative 1994-1995 cohort of families with twins. Bullied and nonbullied MZ twins showed distinct patterns of cortisol secretion after the PST. Specifically, bullied twins exhibited a blunted cortisol response compared with their nonbullied MZ co-twins, who showed the expected increase. This difference in cortisol response to stress could not be attributed to children's genetic makeup, their familial environments, pre-existing and concomitant individual factors, or the perception of stress and emotional response to the PST. Results from this natural experiment provide support for a causal effect of adverse childhood experiences on the neuroendocrine response to stress.

Sex differences in cortisol response to corticotropin releasing hormone challenge over puberty: Pittsburgh Pediatric Neurobehavioral Studies

Consistent sex differences in regulation of the hypothalamic pituitary adrenocortical (HPA) axis have been shown in animal models and emerge over puberty. However, parallel work in humans is lacking despite implications for elucidating the emergence of sex differences in depression over puberty. We investigated sex differences in HPA response to corticotropin releasing hormone (CRH) challenge over puberty in a carefully screened normative sample. Participants were 68 healthy children (41% girls), ages 6-16, with no personal or family history of psychiatric disorder. Pubertal maturation was determined by Tanner staging. Following 24h of adaptation, 9-10 plasma cortisol samples were collected over 30-40 min pre-infusion baseline, 1 μg/kg CRH infusion, and 90-180 min post-infusion recovery. Thirty-seven participants completed 2+ CRH challenges allowing inclusion of cross-sectional and longitudinal data in all analyses. The influence of gender and pubertal maturation on parameters of cortisol response to CRH challenge was investigated using nonlinear mixed model methodology. Girls showed increasing total cortisol output following CRH challenge over puberty, while boys showed little change in total cortisol output over puberty. Increased cortisol output in girls was explained by slower reactivity and recovery rates leading to prolonged time to reach peak cortisol and delayed return to baseline over puberty. Girls also showed increasing baseline cortisol over puberty, while boys showed declining baseline over puberty. Results reveal subtle normative sex differences in the influence of pubertal maturation on HPA regulation at the pituitary level. This normative shift may tip the balance towards stress response dysregulation in girls at high risk for depression, and may represent one potential mechanism underlying elevated rates of depression among pubescent girls.

Comparison of the cortisol responses to testing with two doses of ACTH in patients with suspected adrenal insufficiency

To compare the cortisol response of the 1 μg and the 250 μg ACTH test in a large study of patients with suspected adrenal insufficiency. Retrospective cohort study. Single center study assessing patients tested for primary or secondary adrenal insufficiency between January 2004 and December 2007, who had both ACTH tests (1 μg and 250 μg; n=207) within a time interval of 6 weeks. Test results were compared with a Bland-Altman plot and McNemar's test. The mean difference between the cortisol responses in the two ACTH tests was 26 nmol/l (95% confidence interval (CI) 13, 40), showing a marginally higher response for the 250 μg test. The diagnostic performances of the two tests were similar (P=0.49) using a cut-off value for cortisol of 550 nmol/l. A normal cortisol response to the 1 μg ACTH test could be accompanied by an abnormal response to the 250 μg ACTH test, and vice versa. This study shows that the 1 μg and the 250 μg ACTH tests have comparable cortisol responses in patients with suspected adrenal insufficiency. However, in individual patients, the difference in cortisol response to the two tests can be substantial, and the response in the 250 μg test is not invariably higher than the response in a 1 μg test.

Prenatal maternal emotional complaints are associated with cortisol responses in toddler and preschool aged girls

Associations between prenatal maternal emotional complaints and child behavioral and cognitive problems have been reported, with different relations for boys and girls. Fetal programming hypotheses underline these associations and state that the early development of the HPA-axis of the children may have been affected. In the present study, differences in cortisol responses of prenatally exposed and nonexposed children are examined for both sexes separately. Cortisol response patterns of a group preschool aged children that were prenatally exposed to high levels of maternal emotional complaints (N = 51) were compared to a nonexposed group (N = 52). Child saliva was collected at the start of a home visit (T1), 22 min after a mother-child interaction episode (T2), and 22 min after a potentially frustrating task (T3). Repeated measures analyses showed that prenatally exposed girls showed higher cortisol levels across the three episodes compared to nonexposed girls. No differences were found in boys. Maternal prenatal emotional complaints might be related to child HPA-axis functioning differently for boys and girls.

Individual differences in cortisol responses to fear and frustration during middle childhood

The purpose of this study was to examine individual differences in the activation and regulation of the hypothalamic–pituitary–adrenal (HPA) axis in prepubertal children after exposure to two different stress modalities and to evaluate the utility of an individual differences approach to the examination of HPA axis functioning. After a 30-min controlled baseline period, 73 7-year-olds (40 boys and 33 girls) were randomly assigned to a validity check condition or one of two experimental tasks designed to elicit fear or frustration. This was followed by a 60-min controlled regulation phase. A total of 17 saliva samples were collected, including 12 poststress samples at 5-min intervals. There was a significant stress modality effect, with children exposed to the fear condition reaching peak cortisol levels at 25 min poststress and those exposed to the frustration condition reaching peak levels at 45 min poststress. There was no difference in peak cortisol levels between the stress modalities. Individual variability across conditions was significant, with participants reaching peak levels as early as 10 min poststress and as late as 60 min poststress. Our data suggest that analysis of individual curves prior to making group-level comparisons may improve the explanatory power of HPA axis behavior models.

Sex differences in hormonal responses to a social stressor in chronic major depression

Acute depression has been associated with increased hypothalamic-pituitary-adrenal (HPA) reactivity. While chronicity of depressive illness influences symptoms, course and outcome, its effect on the HPA axis has not been extensively evaluated. The current study evaluated cortisol stress responses to a social challenge in chronic major depressive disorder (CMDD). Cortisol stress responses to the Trier Social Stress Test (TSST) were compared in 26 participants with CMDD and 28 healthy controls using repeated measures analysis of variance (RANOVA). In addition, group differences in area under the curve (AUC) and peak percentage change in cortisol were examined. The RANOVA indicated a significant sex by condition interaction in cortisol responses to the social challenge. Post-hoc testing of pair-wise group differences revealed that in females, CMDD subjects had greater cortisol levels in response to the TSST than did controls. Similarly, AUC was greater in females with CMDD than in female controls. Neither of these differences was significant in males. However, male CMDD subjects exhibited a significantly decreased peak percentage change in cortisol in response to the TSST than did male controls. Males and females with CMDD exhibited unique differences in cortisol responses to the social challenge relative to controls. In females, CMDD subjects had greater overall secretion of cortisol whereas in males, CMDD subjects had a blunted peak response to the social stressor. Sex differences are an important consideration in future work in this population.

Adolescents’ cortisol responses to awakening and social stress; Effects of gender, menstrual phase and oral contraceptives. The TRAILS study

Studies on the influence of sex hormones on cortisol responses to awakening and stress have mainly been conducted in adults, while reports on adolescents are scarce. We studied the effects of gender, menstrual cycle phase and oral contraceptive (OC) use on cortisol responses in a large sample of adolescents. Data come from TRAILS (TRacking Adolescents' Individual Lives Survey), a prospective population study of Dutch adolescents. This study uses data of 644 adolescents (age 15-17 years, 54.7% boys) who participated in a laboratory session including a performance-related social stress task (public speaking and mental arithmetic). Free cortisol levels were assessed by multiple saliva samples, both after awakening and during the laboratory session. No significant effects of gender and menstrual phase on cortisol responses to awakening were found, while girls using OC displayed a slightly blunted response (F(1, 244)=5.30, p=.02). Cortisol responses to social stress were different for boys and free-cycling girls (F(3, 494)=9.73, p<.001), and OC users and free-cycling girls (F(3, 279)=15.12, p<.001). Unexpectedly, OC users showed no response at all but displayed linearly decreasing levels F(1, 279)=19.03, p<.001) of cortisol during the social stress test. We found no effect of menstrual cycle phase on cortisol responses to social stress (F(3, 157)=0.58, p=.55). The absence of a gender difference in the adolescents' cortisol awakening response found in this study is consistent with previous reports. Our results further suggest that adolescent OC users display slightly blunted cortisol responses after awakening, and that gender differences in cortisol responses to social stress during adolescence are comparable to those described for adult populations, that is, stronger responses in men than in women. Whereas previous work in adults suggested blunted stress responses in OC users compared to men and free-cycling women, adolescent OC users showed no cortisol response. Effects of type of OC could not be studied because of low numbers of OC that were only progestin based.

Cortisol response to inoculation in 4-year-old children

This study examined whether there was a cortisol response to inoculation or if pre-inoculation levels were already elevated due to an anticipatory response to going to the doctors' office. For 4-year-old children, a base saliva sample was obtained in the home on a non-stress day, and a pre-inoculation saliva sample was obtained in the doctors' office prior to the stress. Doctors' office pre-inoculation cortisol was higher than home-based cortisol, suggesting the occurrence of an anticipatory cortisol response to the impending stress. Post-inoculation cortisol levels (+20 min) were comparable to home-based cortisol, indicating that there was no cortisol response to the inoculation itself. While there was no mean increase in cortisol, individual differences in cortisol response existed. Cortisol increases were related to important aspects of child behavioral functioning, including internalizing and externalizing behavior ratings.

Caffeine, stress, and proneness to psychosis-like experiences: A preliminary investigation

In diathesis–stress models of psychosis, cortisol released in response to stressors is proposed to play a role in the development of psychotic experiences. Individual differences in cortisol response to stressors are therefore likely to play a role in proneness to psychotic experiences. As caffeine has been found to increase cortisol response to a given stressor, we proposed that, when levels of stress were controlled for, caffeine intake would be related to hallucination-proneness and persecutory ideation. Caffeine intake, stress, hallucination-proneness and persecutory ideation were assessed by self-report questionnaires in a non-clinical sample ( N = 219). Caffeine intake was positively related to stress levels and hallucination-proneness, but not persecutory ideation. When stress levels were controlled for, caffeine intake predicted levels of hallucination-proneness but not persecutory ideation. Implications of these findings are discussed and avenues for future research suggested.

The level of physical activity affects adrenal and cardiovascular reactivity to psychosocial stress

Physical activity plays a key role in the control of neuroendocrine, autonomic, and behavioral responses to physical and psychosocial stress. However, little is known about how the level of physical activity modulates stress responsiveness. Here, we test whether different levels of physical activity are associated with different adrenal, cardiovascular, and psychological responses to psychosocial stress. In addition, competitiveness is assessed as a personality trait that possibly modulates the relationship between physical activity and stress reactivity. Eighteen elite sportsmen, 50 amateur sportsmen, and 24 untrained men were exposed to a standardized psychosocial laboratory stressor (Trier Social Stress Test). Repeated measures of salivary free cortisol, heart rate, and psychological responses to psychosocial stress were compared among the 3 study groups. Elite sportsmen exhibited significantly lower cortisol, heart rate, and state anxiety responses compared with untrained subjects. Amateur sportsmen showed a dissociation between sympathetic and hypothalamic-pituitary-adrenal responsiveness to stress, with significantly reduced heart rate responses but no difference in cortisol responses compared with untrained men. Different levels of competitiveness among groups did not mediate stress reactivity. Our results are in line with previous studies indicating reduced reactivity of the autonomic nervous system to psychosocial stress in trained individuals. More importantly, these findings imply a differential effect of the level of physical activity on different stress-related neurophysiological systems in response to psychosocial stress.

Slower cortisol response during ACTH stimulation test in autistic children

Autism is a hereditary, pervasive neurodevelopmental disorder that starts early in life. The main characteristics of the autism are impairment in social interactions, difficulties in adapting to novel environmental situations and improper reaction to stress. Since the Hypothalamic-Pituitary-Adrenocortical (HPA) axis plays a key role in the response to stress and because the previous research found abnormalities in HPA system, we conducted a study to test several elements of the HPA axis. Because autism is a heritable disorder, autistic subjects were studied as well as their parents. Cortisol circadian rhythm, cortisol daily secretion and its suppression response to dexamethasone had been measured from saliva or urine samples of the autistic children and their parents. Cortisol secretion response after ACTH stimulation was done with the autistic children only. The cortisol elevation after ACTH stimulation among the autistic individuals was slower (P = 0.017) than in healthy controls. No differences were found in salivary cortisol circadian rhythm or suppression response, as well as in cortisol daily excretion. These data indicate that, compared to healthy subjects, autistic individuals have fine differences in cortisol response to ACTH stimulation or possibly to other types of stress.

Differences in cortisol response affect the distinction of observed reactive and proactive aggression in children with aggressive behaviour disorders

Various researchers distinguished two categories of aggressive behaviour, namely reactive and proactive aggression. Reactive aggression is an aggressive response to a perceived threat or provocation, whereas proactive aggression is behaviour that anticipates a reward. In the present study, including both a sample of disruptive behaviour disordered (DBD) and normal control (NC) children, we observed reactive and proactive aggressive behaviour during an experimental dyadic play session. DBD children showed more observed reactive and proactive aggression. Subsequently, we investigated whether the observed measures correlated with parent-rated measures of reactive and proactive aggression in. We distinguished in both NC and DBD children a subgroup showing a rise in cortisol level, i.e. responders, and a subgroup who did not show a rise in cortisol, i.e. non-responders. Results suggest that differences in the cortisol response affects the correspondence between observed and parent-rated reactive and proactive aggression since only DBD non-responders showed the expected correlations.

Cortisol responses to psychological stress in adults after prenatal exposure to the Dutch famine

Experimental studies in animals show that prenatal undernutrition leads to lifelong alterations in the activity of the hypothalamic-pituitary-adrenal (HPA) axis. Some studies have shown associations between low birth weight and an increased HPA response to psychological stress. We tested the hypothesis that prenatal exposure to the Dutch 1944-1945 famine leads to an elevated HPA response to psychological stress in adult life. We measured salivary cortisol responses to a psychological stress protocol among 694 adults who were born as term singletons in Amsterdam, the Netherlands, around the time of the 1944-1945 Dutch famine. We compared cortisol profiles of participants exposed to famine during late (n=120), mid (n=100), or early gestation (n=62) to profiles of participants unexposed to famine during gestation (n=412). The mean increase in cortisol concentrations from baseline was 30% (95% CI 23-37). There were no statistically significant differences in the mean profile of cortisol response to the psychological stress protocol between participants exposed and unexposed to famine in utero. The mean sex and BMI adjusted difference in cortisol response for those exposed compared to those unexposed was -6% (95% CI: -15 to 2). The cortisol profiles of those exposed in late (-4% [95% CI: -16 to 7]), mid (-9% [95% CI: -22 to 3]) or early gestation (-4% [95% CI: -20 to 10]) did not differ from the profile of those unexposed to famine. We conclude that prenatal exposure to famine does not seem to be associated with the response of the HPA axis to psychological stress. However, the stress protocol we have used may have been unsuccessful in inducing a strong enough HPA axis activation to be able to detect famine related differences.