Morningness-eveningness and early-morning salivary cortisol levels.

The purposes of this exploratory study were: (1) to describe a 2-h segment of the early-morning salivary cortisol levels of morning (M) and evening (E) types of healthy, day-active adults on one morning; and (2) to compare selected demographic and sleep characteristics. The sample consisted of 20 subjects, aged 23-39 years, 10 of each type. Measures included: morningness-eveningness questionnaire score, demographic information, self-report sleep characteristics, and self-report of well-being. Beginning with time of arising, seven salivary samples were collected at approximately 20-min intervals. Among the sleep variables, bedtime (p = 0.005), time of mid-sleep (p = 0.002), and arising time (p = 0.043) were later in the E group as compared to the M group. Six M and one E subject awoke spontaneously on the morning of sampling without an awakening aid (p = 0.018). Even though total hours of sleep were comparable between groups, E subjects reported feeling less rested in the morning (p = 0.019). Although mean M group salivary cortisol levels were greater than mean E group levels for each sampling time, there were no significant group differences. Eight M subjects reached a sampling period salivary cortisol peak by 50 min after arising, contrasted with six E subjects who reached their peak at that time. These preliminary findings suggest that E types demonstrate lower morning arousal and a delay in their early-morning peak of salivary cortisol relative to M types. Further study is needed to explore the relationship between M and E types, their sleep-wake patterns, and cortisol secretion patterns.     

The effect of stress on salivary cortisol in panic disorder patients.

BACKGROUND: Various findings suggest the possibility of an abnormal cortisol response to CRH in panic disorder patients, which raises the question of whether such patients might also produce an abnormal cortisol response to stress. The purpose of the present study was to use salivary cortisol measurement in assessing differences in response to novelty/mild stress situations between panic disorder subjects and controls. METHODS: Subjects were recruited by means of posters and subsequently screened for suitability as controls or panic subjects. Twenty-four panic disorder (PD) sufferers and 15 panic-free control subjects were tested on a range of psychometric and physiological measures, at both the start and the end of the experiment. Subjects were tested at the beginning for state anxiety, salivary cortisol, heart rate, and blood pressure, and these tests were repeated at the end of the session (which had been designed to promote reassurance). RESULTS: The state anxiety scores (STAI) showed a reduction in anxiety level over the test period, and there was a corresponding fall in both blood pressure and heart rate for both groups. Cortisol levels also fell over the course of the interview in the control group, but in the PD group cortisol levels showed no such reduction. In addition, there was a significant difference in the levels of cortisol at the start of the session between the two groups (PD group lower). CONCLUSIONS: These data indicate a possible alteration in cortisol responsiveness to stress/novelty situations in PD subjects. This was considered to be consistent with previous suggestions of HPA axis dysregulation in PD patients, although our research indicates unresponsiveness rather than responsiveness to be a factor to be considered for future investigation. CLINICAL IMPLICATIONS: Our results suggest that not all subjects suffering PD may benefit from stress reduction therapies as a first choice of treatment for their panic attacks. The existence of nocturnal panic attacks (considering sleep as a combination of mental and physical relaxation), in the absence of nightmares, as well as the induction of panic attacks during relaxation support this view. LIMITATIONS OF THE STUDY: Apart from the difficulty in accessing sufficient symptomatic subjects, the induction of higher levels of stress could be useful for confirmation of these results. However, this requires specialist support in case of subjects developing panic attacks during the experiments, which was not available during the present study. SUMMARY: Twenty-four panic disorder (PD) sufferers and 15 panic-free control subjects were tested on a range of psychometric and physiological measures, at both the start and the end of an experimental session. Subjects were tested at the beginning for state anxiety, salivary cortisol, heart rate, and blood pressure, and these tests were repeated at the end of the session. The state anxiety scores (STAI) showed a reduction in anxiety level over the test period for both groups, and there was a corresponding fall in both blood pressure and heart rate. Cortisol levels also fell over the course of the session in the control group, but in the PD group cortisol levels showed no such reduction. In addition, there was a significant difference in the levels of cortisol at the start of the session between the two groups (PD group lower). These data indicate a possible alteration in cortisol responsiveness to stress/novelty situations in PD subjects. This was considered to be consistent with previous suggestions of HPA axis dysregulation in PD patients, although our research indicates unresponsiveness rather than responsiveness to be a factor to be considered for future investigation.     

Study of salivary cortisol using radioimmunological assay. Diagnostic value

Salivary cortisol levels reflect the biologically active "free" fraction of blood cortisol. The authors describe the results obtained with the aim of a radio-immunoassay commercial serum cortisol kit, without prealable extraction in different physiological and pathological situations. Salivary cortisol determination appears performant both in nycthemeral studies and in stimulation or freination tests.     

Relationship of serum serotonin and salivary cortisol with sensation seeking

The present study was conducted to investigate the possible relationship of serum serotonin and salivary cortisol with the sensation seeking (SS) trait. Blood and saliva samples were taken from 57 male volunteers (mean age 23 ± 5 years) to measure serum serotonin and salivary cortisol concentrations. Zuckerman's Sensation Seeking Scale (SSS-V) was used to assess SS. Pearson's correlation coefficient revealed that high serum serotonin levels did not correlate significantly with low SS scores (r = 0.12). However, a negative correlation between SS scores and salivary cortisol levels (r = − 0.34, p < 0.01) was significant, suggesting that high SS scores are related to low concentrations of salivary cortisol. The negative correlation between salivary cortisol and SS is clearly compatible with the optimal level of Catecholamine system activity (CSA), component of SS theory, indicating that high sensation seekers (HSSers) tend to seek excitement and novelty to compensate for the shortage of CSA achieving optimal arousal. Further investigation is needed before conclusions can be drawn regarding the relationship of serum serotonin and SS.     

Social support and salivary cortisol in women with metastatic breast cancer

OBJECTIVE: This study used a cross-sectional design to examine the relationships between social support, both quantity (number of people) and quality (appraisal, belonging, tangible, and self-esteem), and neuroendocrine function (mean and slope of diurnal salivary cortisol) among women with metastatic breast cancer. METHODS: Participants (N = 103) were drawn from a study (N = 125) of the effects of group therapy on emotional adjustment and health in women with metastatic breast cancer. They completed the Interpersonal Support Evaluation List and the Yale Social Support Index and provided saliva samples for assessment of diurnal cortisol levels on each of 3 consecutive days. Diurnal mean levels were calculated using log-transformed cortisol concentrations, and the slope of diurnal cortisol variation was calculated by regression of log-transformed cortisol concentrations on sample collection time. RESULTS: Mean salivary cortisol was negatively related to the Interpersonal Support Evaluation List subscales of appraisal, belonging, and tangible social support. No association was found between quantitative support or the esteem subscale of the Interpersonal Support Evaluation List and mean salivary cortisol. Measures of qualitative and quantitative social support were not associated with the diurnal cortisol slope. CONCLUSIONS: Results show that greater quality of social support is associated with lower cortisol concentrations in women with metastatic breast cancer, which is indicative of healthier neuroendocrine functioning. These results may have clinical implications in the treatment of breast cancer.     

Effect of hostility on salivary cortisol levels in university students

The influence of hostility on cortisol levels in saliva was investigated in 47 university students (27 males and 20 females). The students were divided into high and low hostility groups by cluster analyses based on their scores on the Buss-Perry Aggression Questionnaire and the Müller Anger Coping Questionnaire. Their saliva was collected twice, in the morning immediately after awakening at a two week interval. On the day before saliva collection, they completed questionnaires about stressful events and their moods in the previous two weeks. The results of the ANOVA showed higher cortisol levels and higher frequencies of stressful events and negative moods in the high hostility group. The effect of hostility on cortisol levels was diminished by controlling for stressful events and negative moods, which suggests that stressful events and negative moods are mediators between hostility and cortisol. The results are discussed in relation to the association between hostility and coronary heart disease.     

The impact of abbreviated progressive muscle relaxation on salivary cortisol

The purpose of this study was to examine whether acute relaxation training, conducted on two separate occasions, would be associated with reliable reductions in subjective and physiological indices of stress. Forty-six experimental subjects were led through Abbreviated Progressive Relaxation Training (APRT) exercises during two laboratory sessions spaced exactly 1 week apart. Fifteen control subjects experienced two laboratory sessions where they sat quietly for an equal amount of time. Results indicated that a brief relaxation exercise led to experimental subjects having significantly lower levels of post-intervention heart rate, state anxiety, perceived stress, and salivary cortisol than control subjects, as well as increased levels of self-report levels of relaxation. The results of this study may have implications for the use of relaxation training in enhancing immune function.     

Differences in salivary cortisol levels in cocaine-exposed and noncocaine-exposed NICU infants.

To assess whether cocaine exposure in utero affected adrenocortical responsiveness in the neonatal period, salivary cortisol levels were compared between noncocaine-exposed (n = 35) and cocaine-exposed (n = 11) healthy preterm infants just prior to hospital discharge. Cortisol levels were measured under three conditions: Basal--120 min after no disrupting event or behavioral distress; Noninvasive Stressor--30 min after a neurobehavioral examination; Invasive Stressor--30 min after a heel-stick procedure. There were no differences in Basal cortisol levels between the noncocaine-exposed and cocaine-exposed infants, but the cocaine-exposed infants had significantly lower levels in both the Noninvasive and Invasive Stressor conditions. The suppressed cortisol responding to stressful events in cocaine-exposed infants suggests that these infants may have decreased modulation capability to normally stressful events, which could underlie some of the subtle state regulation problems reported.     

Cloning and expression of a Streptococcus sanguis surface antigen that interacts with a human salivary agglutinin.

Human saliva contains a high-molecular-weight glycoprotein (agglutinin) which binds to specific streptococci in a calcium-dependent reaction leading to the formation of bacterial aggregates. We report the cloning of a gene encoding a surface antigen from Streptococcus sanguis M5 and show that the expressed protein inhibits agglutinin-mediated aggregation and specifically binds the salivary agglutinin in a calcium-dependent fashion. Clones isolated from the immunological screening of S. sanguis M5 genomic libraries with polyclonal antibodies against whole cells were assayed for the ability to compete with S. sanguis for agglutinin. One clone, pSSP-5, expressed antigens of 165 and 130 kilodaltons (kDa) possessing this activity. A 3-kilobase-pair (kbp) insert fragment from this clone was used to screen a genomic library in lambda EMBL3 which resulted in the isolation of clone SSP-5A. This clone contained an insert of 17 kb and expressed proteins of 170 to 205 kDa that reacted with the anti-S. sanguis antibodies. Subcloning of a 5.3-kbp EcoRI-BamHI fragment from SSP-5A produced pEB-5, which expressed streptococcal components that were indistinguishable from SSP-5A. The streptococcal antigen was purified by gel permeation and ion exchange chromatography and shown to potently compete with S. sanguis M5 cells for agglutinin. The antigen also bound purified salivary agglutinin in the presence of 1 mM CaCl2. This binding was inhibited by EDTA. Both the SSP-5 antigen and a 205-kDa protein in surface protein extracts from S. sanguis M5 cross-reacted with antibodies directed against antigen B from S. mutans and SpaA from S. sobrinus 6715. These results indicate that a 205-kDa surface protein that is antigenically related to SpaA and antigen B is involved in the binding of salivary agglutinin to S. sanguis M5.     

Effect of flavored beverage crystals on salivary cortisol enzyme-immunoreactive assay measurements

We examined the effects of using flavored drink crystals as a salivary stimulant on salivary cortisol values. The effects of both amount and method of flavored crystal administration on cortisol values were evaluated using a high sensitivity enzyme immunoassay (EIA) kit to measure cortisol. Repeated saliva sampling, one sample without the drink crystal stimulant, followed immediately by a second sample using the drink crystal stimulant, allowed direct analysis of the effect of the stimulant on cortisol values. Repeated sampling, with the stimulant used when obtaining both the first and second samples, allowed analysis of the repeatability of cortisol measurements using the drink crystals. The results suggest that the use of drink mix crystals as an oral stimulant causes a small increase in measured cortisol values, as well as an increase in the variability of these values. The results also suggest that the effect of drink crystals is sufficiently regular so that it will not distort either within or between subject comparisons as long as there is consistency in use or non-use of the stimulant.     

GABA interacts with photic signaling in the suprachiasmatic nucleus to regulate circadian phase shifts

Circadian rhythms of physiology and behavior in mammals are driven by a circadian pacemaker located in the suprachiasmatic nucleus of the hypothalamus. The majority of neurons in the suprachiasmatic nucleus are GABAergic, and activation of GABA receptors in the suprachiasmatic nucleus can induce phase shifts of the circadian pacemaker both in vivo and in vitro. GABA also modulates the phase shifts induced by light in vivo, and photic information is thought to be conveyed to the suprachiasmatic nucleus by glutamate. In the present study, we examined the interactions between GABA receptor agonists, glutamate agonists, and light in hamsters in vivo. The GABA(A) receptor agonist muscimol and the GABA(B) receptor agonist baclofen were microinjected into the suprachiasmatic nucleus at circadian time 13.5 (early subjective night), followed immediately by a microinjection of N-methyl-D-aspartate (NMDA). Both muscimol and baclofen significantly reduced the phase shifting effects of NMDA. Further, coadministration of tetrodotoxin with baclofen did not alter the inhibition of NMDA by baclofen, suggesting a postsynaptic mechanism for the inhibition of NMDA-induced phase shifts by baclofen. Finally, the phase shifting effects of microinjection of muscimol into the suprachiasmatic nucleus during the subjective day were blocked by a subsequent light pulse. These data suggest that GABA regulates the phase of the circadian clock through both pre- and postsynaptic mechanisms.     

Executive functioning, cortisol reactivity, and symptoms of psychopathology in girls with premature adrenarche

The study examined the interaction between early maturational timing (measured by premature adrenarche [PA]) and executive functioning and cortisol reactivity on symptoms of psychopathology. The study included 76 girls aged 6 through 8 years (mean = 7.50, SD = 0.85) with PA (n = 40) and on-time adrenarche (n = 36). Girls completed a battery of psychological and neuropsychological tests and blood sampling for cortisol. Parents completed the Child Behavior Checklist. The results demonstrated that girls with PA with lower levels of executive functioning had higher externalizing and anxious symptoms compared to other girls. In addition, girls with PA who demonstrated increases in serum cortisol had higher externalizing symptoms than those with stable patterns. Finally, girls with PA who demonstrated decreases in cortisol reported higher depressive symptoms. The findings from this study provide important information concerning the impact of cognitive functioning and stress reactivity on adjustment to early maturation in girls with PA. The results of this research may inform screening and intervention efforts for girls who may be at greatest risk for emotional and behavioral problems as a result of early maturation.     

Growth hormone and cortisol responses, tranquillizer usage, and their association with survival from myocardial infarction.

Sixty-six patients consecutively admitted to a Coronary Care Unit with a diagnosis of myocardial infarction were evaluated physically, psychologically, and neuroendocrinologically. Records were also kept of appetite and drug intake. Serum cortisol and growth hormone, physical, and mood variables were evaluated daily and the neuroendocrine measures were also taken serially at the time of removal from the cardiac monitor. At the end of the 2 years the patient's functional status was evaluated and the outcome correlated with the aforementioned indices. Three factors emerged as being significantly related to outcome. Survivors' appetites were significantly better than the appetities of nonsurvivors. Those who were alive at follow-up had taken significantly more minor tranquilizers than those who had died. Survivors had consistently lower levels of growth hormone than nonsurvivors and these differences were statistically significant for those samples taken at the time of removal from the monitor. The findings are incorporated in two new indices predictive of both survival and functional outcome.     

Emotional bias and waking salivary cortisol in relatives of patients with major depression

BACKGROUND: Biases in the processing of emotional information have been shown to be abnormal in subjects with major depression, both during an episode and after full recovery. However, it is unclear whether these biases are a cause or an effect of the depression. This study set out to explore whether such biases represent a vulnerability factor for depression by looking at unaffected first-degree relatives of those with major depressive disorder. We also measured waking salivary cortisol, as the regulation of the hypothalamo-pituitary-adrenal (HPA) axis is thought to be impaired in depressive disorder. METHOD: Twenty-five female relatives and 21 age-matched controls completed a facial expression recognition task, an emotional categorization task with positive and negative personality characteristics, and had their waking salivary cortisol measured on a work day and a non-work day. RESULTS: The depressed relative group was significantly faster to recognize facial expressions of fear than controls. The depressed relative group also showed significantly increased reaction time to recognize positive versus negative personality characteristics in the categorization task. There was no difference in waking salivary cortisol between groups, although there was an effect of work day versus non-work day. CONCLUSIONS: Subtle biases in the processing of emotional information may exist in the unaffected first-degree relatives of those with depression. As such, this may represent a familial vulnerability factor to developing a depressive illness.     

Influences of premenstrual syndrome on daily psychological states and salivary cortisol level

The purpose of this study is to investigate the influences of premenstrual syndrome (PMS) on daily psychological states and salivary cortisol level. First, 42 women recorded their PMS symptoms and basal body temperatures every day for approximately two menstrual cycles. Based on these prospective records of PMS symptoms, participants were divided into two groups: Normal group (n=22) and PMS group (n=17). There were no significant differences between the two groups in age, height, weight, age at menarche, menstrual cycle length, menstrual period, depression score, and stressor score. Next, 14 women (7 Normal group, 7 PMS group) were selected and they were measured twice, once during the premenstrual phase and once during the postmenstrual phase of their cycles. Each day, they took saliva samples and recorded their psychological states six times (from waking to going to bed) per day at their homes. Results showed that the fear score in PMS group was high in the premenstrual phase, whereas salivary cortisol level in PMS group was low in the same phase compared to the Normal group. These results suggested the possibility of dysregulation of the stress system in women with PMS.     

Analysis of circadian periodicity of plasma cortisol in normal man and in Cushing's syndrome.

In normal subjects, adjusted to a circadian environment, half-hourly plasma cortisol levels over a 24-h span (time series, TS) outline a circadian sinusoidal pattern that may be masked by superimposed short-lived oscillations. The periodogram objectively defines the features (amplitude, phase) of this pattern in individual TS and, more efficiently, in the average and concatenation of homogeneous TS. Concatenation is a procedure by which homogeneous short TS are attached one after the other. Homogeneity is inferred by variance analysis and by a new measure, h, with statistical significance, derived from the spectrum of the concatenated TS. Through concatenation, autocovariance for periodicity identification becomes possible. The TS from three groups of volunteers are highly homogeneous and have a predominant, statistically significant amplitude with peak time near 1100 h. The patterns from patients with Cushing's disease differ markedly in their means and periodic features; by the above criteria, we identify a subgroup with significant h measure and 24-h amplitude. This analysis provides a tool for investigation of the circadian clock in man.     

Changes in salivary cortisol levels as a prognostic predictor in children with anorexia nervosa

This study investigated the hypothalamus-pituitary-adrenal (HPA) axis activity in children with anorexia nervosa (AN) before and after inpatient treatment. Salivary cortisol levels were measured to ascertain whether changes in the HPA axis activity following therapeutic intervention could be applicable as a prognostic predictor. This study comprised 21 females with AN and 22 control subjects. Saliva was collected at 2-hour intervals from 9 a.m. to 7 p.m. before and after inpatient treatment. The concentrations for areas under the curve (AUC) were compared with physical parameters, eating attitude score, profile of mood states (POMS), and prognostic factors. Mean salivary cortisol levels at all points and mean AUC cortisol levels in subjects with AN before therapy were significantly higher than those in controls, but returned to control levels after inpatient treatment. Higher AUC cortisol levels were associated with lower standard deviation for weight in AN. A significant positive correlation between the AUC cortisol level and POMS subscale of “Fatigue” was apparent in the control group, but not in the AN group. The increased change values of AUC cortisol level before and after inpatient treatment correlated with increased body weight gain ratio just after treatment, but not with the ratio after one year. The present study indicated that HPA axis activity could reflect severity of illness, but did not show an accurate neuroendocrine response for mood states. Changes in HPA axis activity following treatment could therefore be used to predict prognosis and particularly in the short term.