Increase in concentration of waking salivary cortisol in recovered patients with depression

OBJECTIVE: Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis with elevated plasma cortisol levels is characteristic of acute major depression. However, it is unclear whether HPA axis abnormalities are present in fully recovered patients. An increase in salivary cortisol levels after waking provides a simple, dynamic measure of HPA axis activity. The authors measured this increase in recovered depressed patients and in a healthy comparison group. METHOD: Salivary cortisol levels were measured upon waking and at 15-minute intervals for the next hour in 31 medication-free, recovered depressed patients and in 31 matched healthy comparison subjects. RESULTS: The increase in salivary cortisol levels that followed waking was significantly higher in the patients. CONCLUSIONS: Greater secretion of cortisol may be present in depressed subjects after clinical recovery and withdrawal of medication. This may put patients at risk of further episodes of depression as well as comorbid medical conditions, such as coronary heart disease.     

A meta-analysis of blood and salivary cortisol levels in first-episode psychosis and high-risk individuals

Dysregulated cortisol responses and glucose metabolism have been reported in psychosis. We performed a random-effects meta-analysis of cortisol responses in first-episode psychosis (FEP) and psychosis risk states, taking into consideration glucose metabolism. A total of 47 studies were included. Unstimulated blood cortisol levels were significantly higher (g = 0.48, 95 %CI: 0.25–0.70, p < 0.001) in FEP, but not in psychosis risk states (g = 0.39, 95 %CI: −0.42–1.21, p = 0.342), compared to controls. Cortisol awakening response (CAR) was attenuated in FEP (g = −0.40, 95 %CI: −0.68 - −0.12, p = 0.006), but not in psychosis risk states (p = 0.433). Glucose and insulin levels were positively correlated with unstimulated blood cortisol levels in FEP. Our meta-analysis supports previous findings of elevated blood cortisol levels and attenuated CAR in FEP. Future research should focus on identifying the common denominators for alterations in stress hormones and glucose metabolism.     

Correlation of salivary cortisol level with obstructive sleep apnea syndrome in pediatric subjects

Objective

Obstructive sleep apnea syndrome (OSAS) is associated with stress system activation involving the hypothalamic–pituitary–adrenocortical (HPA) axis. The relationships among salivary cortisol, a measure of the HPA axis, and objective parameters of polysomnography (PSG) and subjective sleep symptoms were examined.

Methods

Our prospective study enrolled 80 children who had a physical examination, underwent overnight PSG, and completed the Korean version of the modified pediatric Epworth sleepiness scale (KMPESS) and OSA-18 (KOSA-18) questionnaires. Saliva was collected at night before PSG and in the early morning after PSG.

Results

Subjects (N = 80) were divided into control (n = 32, apnea–hypopnea index [AHI] < 1) and OSAS (n = 48, AHI ? 1) groups; the OSAS group was subdivided into mild (1 ? AHI < 5) and moderate to severe (AHI ? 5) groups. Although salivary cortisol before PSG (n-sCor) did not show a significant change with OSAS severity, salivary cortisol after PSG (m-sCor) significantly decreased with OSAS severity. This decrease resulted in a salivary cortisol ratio (r-sCor) that was significantly different between the control group and the two OSAS subgroups. The m-sCor and sub-sCor of the total group as well as the m-sCor, sub-sCor, and r-sCor of the OSAS group were negatively related to the oxygen desaturation index (ODI). The m-sCor and r-sCor in the OSAS group also were related to subjective sleep symptoms (quality of life [QOL] by KOSA-18).

Conclusions

Among the four salivary cortisol parameters, r-sCor was negatively associated with OSAS severity, ODI, and QOL (KOSA-18), which may indicate a chronically stressed HPA axis. These results demonstrate that salivary cortisol may be a useful biomarker of OSAS.     

Hippocampal formation volume, memory dysfunction, and cortisol levels in patients with Cushing's syndrome.

Patients with chronic hypercortisolemia due to Cushing's syndrome (CS) exhibit cognitive dysfunction. Because glucocorticoid excess is associated with hippocampal damage in animals, and the hippocampus participates in learning and memory, we explored the relationships between hippocampal formation (HF) volume, memory dysfunction, and cortisol levels in 12 patients with CS. After magnetic resonance imaging, HF volume was determined using digital sum of track ball traces of dentate gyrus, hippocampus proper and subiculum, correcting for total intracranial volume. For 27% of the patients, HF volume fell outside the 95% confidence intervals for normal subject volume given in the literature. In addition, there were significant and specific correlations between HF volume and scores for verbal paired associate learning, verbal recall, and verbal recall corrected for full-scale IQ (r = 0.57 to 0.70, p < 0.05). HF volume was negatively correlated with plasma cortisol levels (r = -0.73, p < 0.05). These studies suggest an association between reduced HF volume, memory dysfunction, and elevated cortisol in patients with CS.     

Changes in salivary cortisol levels in pediatric patients with obstructive sleep apnea syndrome after adenotonsillectomy

ObjectiveObstructive sleep apnea syndrome (OSAS) activates the stress response system, including the hypothalamic–pituitary–adrenocortical (HPA) axis. The salivary cortisol, as an index of free circulating cortisol levels, may be used as a measure of HPA axis activity. We examined the change in the salivary cortisol level in pediatric OSAS patients before and after adenotonsillectomy (AT).MethodsForty-eight subjects from 80 subjects suspicious of having OSAS were diagnosed with OSAS by overnight PSG, 34 of 48 OSAS patients undergoing AT, and 13 of 34 OSAS patients were finally enrolled prospectively for this study. Before and three months after the AT, the saliva was collected at night before PSG (n-sCor) and in the early morning after PSG (m-sCor) for the measurements of the salivary cortisol level.ResultsChildren in the study population (n = 13) were divided into mild (1⩽ AHI <5, n = 5), moderate (5⩽ AHI <10, n = 3), and severe (AHI ⩾10, n = 5) OSAS groups. The mean preoperative AHI in the children was 14.7, and the mean postoperative AHI was 0.33. The percentage of children with AHI <1 after AT was 92.3%. Postoperative m-sCor, the difference of cortisol level (sub-sCor: m-sCor minus n-sCor), and the ratio of cortisol level (r-sCor: m-sCor/n-sCor) showed significant difference postoperatively.ConclusionsAT was associated with improvements in PSG and subjective symptoms in pediatric OSAS patients. In addition, these improvements were significantly related to normalization of salivary cortisol level after AT. Although further study on salivary cortisol levels needs to be done, the measurement of salivary cortisol level before and after AT may predict the outcome of AT as a treatment of OSAS.     

Laboratory evaluation for Cushing's syndrome in psychiatric patients with cortisol nonsuppression following the overnight dexamethasone suppression test

Laboratory tests used for the differential diagnosis of Cushing's syndrome have infrequently been employed in investigations of psychiatric patients who demonstrate hypothalamic-pituitary-adrenal (HPA) overactivity, and these laboratory procedures have not previously been applied for the specific purpose of further evaluating the endocrine function of psychiatric patients with serum cortisol nonsuppression following the standard 1-mg overnight Dexamethasone Suppression Test (DST). Low-dose (4 mg/48 hr) and high-dose (16 mg/48 hr) DSTs were administered to 10 psychiatric patients who exhibited cortisol nonsuppression after the overnight DST. Patients all had normal suppression to both the low-dose and high-dose tests. HPA overactivity in these patients was thus not sufficient to meet laboratory criteria for the diagnosis of Cushing's syndrome. Study results suggest that psychiatric patients with abnormal cortisol suppression following the 1-mg overnight DST are likely to have normal responses when assessed by standard laboratory protocols used for the diagnosis of Cushing's syndrome.     

Severe myopathy and psychosis in a patient with Cushing's disease macroadenoma

Cushing's disease is most commonly caused by a corticotrope adenoma of the pituitary. Between 50 and 70% of patients with spontaneous hypercortisolism have ACTH-producing pituitary adenomas. The tumors are usually microadenomas with approximately 20% of patients with the disease showing no evidence of tumor on CT-scans or MR imaging of their pituitary glands. In contrast to patients with ectopic ACTH production, plasma ACTH concentrations in patients with spontaneous disease are generally within the normal range. We describe here a patient with a pituitary macroadenoma that showed evidence of necrosis on MRI. The patient had an atypical clinical presentation with plasma ACTH levels considerably higher than that seen in patients with non-ectopic ACTH-secretory syndrome, markedly elevated urine free cortisol, lack of phenotypical signs of hypercortisolism such as wide purplish striae, and whose most prominent and distressing symptom was severe myopathy that resulted in the patient becoming bed-ridden. Psychosis was another striking feature in this patient who during his hospital course developed multiple opportunistic infections that contributed to his demise.     

Cushing's syndrome after treatment: changes in cortisol and ACTH levels, and amelioration of the depressive syndrome

Twenty-three patients with pituitary adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome were studied before and after treatment. The relationship between the amelioration of the depressive syndrome and changes in cortisol and ACTH levels was investigated. There was a significant difference in mean change in 24-hour urinary free cortisol (UFC) excretion for changes in the depressed mood score from first to last visit. There were also significant correlations between decreases in UFC and decreases in both the depressed mood score and the modified Hamilton depression score. These relationships were not found for ACTH. Furthermore, with cortisol decreased to normal levels, continued high ACTH levels did not prevent improvement in depressed mood. The possibility that cortisol may also play a role in the pathogenesis and/or maintenance of the mood disorder in psychiatric patients is discussed.     

Evoked potential correlates of psychosis

Evoked potential (EP) correlates of several psychiatric disorders were investigated by applying a comprehensive EP procedure to 102 psychiatric patients and 28 nonpatients. EPs to left and right median nerve shocks, visual pattern flashes, and auditory clicks were recorded from one EOG and 14 monopolar scalp derivations. Nine age- and sex-matched groups were compared to yield the following main results: (i) EPs of overtly psychotic patients (schizophrenics, depressives, manics) differed markedly from normal, while those of patients without overt psychosis (neurotics, personality disorders, latent schizophrenics) did not; in the overtly psychotic, later EP events (100 msec or more poststimulus) were attenuated. (ii) EPs of neurotic depressives differed greatly from those of psychotic depressives. (iii) A somatosensory negative peak occurring 60-msec poststimulus (N60) was more posteriorly distributed in chronic schizophrenics (paranoid, undifferentiated) than in any other subject group. The attenuated later EP activity associated with overt psychosis was interpreted as a concomitant of cognitive (attention?) impairment, rather than of emotional disturbance.     

Nicotine use and its correlates in patients with psychosis

OBJECTIVE: To examine nicotine use and its correlates among psychotic patients. METHOD: Longitudinal naturalistic study of 176 patients, diagnosed with schizophrenia or schizophrenia-related psychotic disorders, and treated with risperidone at study entry. Levels of nicotine use (smoking, snuffing) were measured along with other relevant ratings and measurements (symptoms, drug treatment, side effects, weight, cognitive functions and outcome) at baseline and once yearly for 5 years. RESULTS: Nicotine use was twice as common as in the general population. Only few nicotine users had started after onset of psychoses. We could not find any differences among nicotine users and non-users in diagnosis, symptoms, side effects, weight, cognitive functions, personality and outcome, cross-sectionally and longitudinally, ruling against the 'self-medication' hypothesis. CONCLUSION: A parsimonious interpretation of the findings is that patients suffering from psychosis fail to desist from nicotine rather than experience significant positive effects of the usage.     

Increased diurnal salivary cortisol in women with borderline personality disorder

Borderline personality disorder (BPD) is characterized by a pervasive pattern of instability in affect regulation, impulse control, interpersonal relationships, and self-image. In previous studies, we have used portable mini-computers to assess the severity of recurrent states of aversive emotional distress and dissociation during ambulatory conditions. Here, we used this approach for the assessment of the hypothalamic–pituitary–adrenal (HPA) axis in patients with BPD. We studied 23 unmedicated female patients with BPD and 24 matched healthy controls. Salivary cortisol was collected from all participants during ambulatory conditions in response to reminders provided by portable mini-computers on 3 consecutive days every 2 h for 14 h after awakening. In addition, cortisol in response to awakening was determined in four 15 min intervals on days 1 and 2. After the last collection of cortisol on the second day, 0.5 mg dexamethasone was administered in order to achieve cortisol suppression on day 3 (low-dose dexamethasone suppression test, DST). Patients with BPD displayed significantly higher salivary cortisol levels than healthy controls as demonstrated by higher total cortisol in response to awakening and higher total daily cortisol levels. There were significantly more non-suppressors of cortisol in the low-dose DST in the patient group when compared to the control group. The ambulatory assessment of saliva cortisol is a suitable approach to study basic parameters of the HPA-axis in patients with BPD. Increased adrenal activity and lowered feedback sensitivity of the HPA-axis may characterise BPD. Further studies have to reveal reasons of heightened adrenal activity in these patients.     

Cognitive decline in patients with Cushing's syndrome.

Chronic exposure to elevated glucocorticoid levels in Cushing's syndrome (CS), is associated with deficits in cognitive function and in emotion. The hippocampus plays a crucial role in the behavioral manifestations of the syndrome as it is richest in glucocorticoid receptors and is thus particularly vulnerable to glucocorticoid excess. The wide distribution of glucocorticoid receptors throughout the cerebral cortex, however, suggests that several cognitive functions can also be affected by the dysregulation of glucocorticoids. In this study, we investigated how an excess of glucocorticoid hormones affects cognitive processes. Nineteen patients with chronic hypercortisolemia due to CS were compared to healthy controls matched for age, sex, education, and occupation in tests of processing of visual and spatial information, memory, reasoning and concept formation, language and verbal functions, and attention. Multivariate and univariate analyses revealed overall differences in tests of treatment of visual and spatial information, reasoning and concept formation as well as in verbal and language performance, with poorer performance from CS patients. Differences were also observed in nonverbal aspects of memory and in attention tasks. The results suggest that chronic exposure to elevated levels of cortisol is associated with deficits in several areas of cognition, particularly those involving processing of selective attention and visual components. This study also shows that hormones play an important role in the modulation of cognitive function and that their influence on cerebral structure and function merits closer scrutiny.     

The morning salivary cortisol response in burnout

OBJECTIVES: The aim of the present study was to examine the free salivary cortisol response to awakening in men and women reporting low, moderate, and high levels of burnout. METHODS: Twenty-two patients on sick leave due to burnout were compared with 22 working participants with low and 20 working participants with intermediate scores on the Shirom-Melamed Burnout Questionnaire (SMBQ), with regard to the free salivary cortisol response to awakening. Saliva samples were collected upon awakening and at +15, +30, and +60 min thereafter. RESULTS: Female burnout patients had higher cortisol levels than did the females with low burnout at awakening and at +15, +30, and +60 min after awakening. They also had a greater area under the curve (AUC) for salivary cortisol than did the female participants with low burnout. Male participants with moderate levels of burnout had higher cortisol levels at +60 min after awakening compared with males with low burnout. CONCLUSIONS: The results of the present study indicate a dysregulation in hypothalamic-pituitary-adrenocortical axis (HPA axis) activity, characterised by elevated morning salivary cortisol levels, among female burnout patients. Among males, increased cortisol levels were observed among participants with moderate levels of burnout, but not among patients or healthy controls.     

Enhanced early morning salivary cortisol in neuroticism

OBJECTIVE: Neuroticism is a predisposing factor for major depression. The increase in salivary cortisol that follows waking provides a reliable measure of adrenocortical activity, and this response is increased in recovered depressed patients. This study compared waking cortisol levels in healthy subjects with high and low levels of neuroticism without a previous history of depression. METHOD: Salivary cortisol levels were measured upon waking and at 15-minute intervals for the next hour in volunteers selected to have high (>19/23) or low (<4/23) neuroticism based on the Eysenck Personality Inventory. RESULTS: Subjects with high neuroticism showed significantly greater levels of salivary cortisol 30 minutes after waking, which were maintained for the next half hour. CONCLUSIONS: Abnormalities in waking cortisol are associated with neuroticism in a way similar to those seen in major depression. Elevated waking cortisol may represent a vulnerability marker for mood disorder.     

Diurnal cycles of salivary cortisol in older adults

Cortisol has a well-documented circadian pattern. However, recent studies have demonstrated that individual variation in diurnal cortisol patterns occurs in young adult populations. Since older adults experience altered sleep-wake cycles and changes in circadian rhythmicity, we may see even greater variations in diurnal cortisol patterns in older adults. This study examined salivary cortisol patterns in 48 community dwelling older adults. Participants (mean age 76+/-6) collected saliva every 2 h over a three-day period. Cortisol was assayed by using RIA. Cortisol cycles were defined as inconsistent, typical or flat based on the slopes of two sequential daily cortisol patterns. Demographic, physical, psychological and behavioral measures were tested for group differences using t-tests and chi-square analyses. Forty-eight percent of the sample had inconsistent cycles, 50% had typical cycles and 2% had flat cycles. This sample had a higher percentage of inconsistent cycles and fewer flat cycles than reported for young adults (p=0.008) (Psychoneuroendocrinology 22 (1997) 89). Those with inconsistent cycles were younger and reported higher caffeine and food intake than those with typical cycles. This study demonstrates that normal diurnal rhythms of cortisol can be maintained in older adults, while day-to-day variation may increase.     

Neuroticism and introversion are associated with salivary cortisol patterns in adolescents

Previous studies have yielded equivocal findings on the relationship between personality and cortisol activity. The present study examined associations between personality and cortisol activity in a large, diverse adolescent sample, while partialling the effects of relevant demographic and health-related covariates. A subsample of 230 participants (57% of whom reported elevated neuroticism) was selected from a larger sample of 16-18-year olds involved in a study on risk factors for emotional disorders. Subsample participants completed a battery of personality questionnaires, and saliva collection was requested several months later on three consecutive days at six time points per day, from wakeup to bedtime. Associations between personality and cortisol rhythms were examined using multilevel growth curve modeling. Neuroticism (N) and introversion (I) were significantly and differentially associated with features of diurnal cortisol patterns. Specifically, a significant N x gender interaction was observed, demonstrating flatter cortisol rhythms across the waking day among male participants with higher N. Elevated I, however, was associated with lower cortisol awakening responses for both male and female participants, and higher cortisol at the time of waking for male participants only. The present study supports personality as a significant predictor of diurnal cortisol patterns in late adolescence, after accounting for the effects of demographic and health covariates, and suggests that gender plays a role in moderating associations between personality and cortisol.