Menopause, mild psychological stress and salivary cortisol: influence of long-term hormone replacement therapy (HRT).

OBJECTIVE: Aim of the present study was to examine the adrenocortical activity in basal condition and following a mild stress exposure in long-term HRT-treated menopausal women. Menopausal women, long term users of HRT (14 subjects) were compared both to menopausal women who had never used HRT (14 subjects) and young pre-menopausal women (14 subjects). STUDY DESIGN: Morning and evening salivary cortisol secretion was measured in samples collected twice a day (08:00 in the morning and 08:00 in the evening). Mild stress response was evoked by administration of the Stroop color-word test (CWT). Salivary cortisol was measured immediately before the start, 15, 30 and 45 min after the completion of the test. RESULTS: Menopause appears not to be associated with an impairment of cortisol circadian fluctuation. Long-term use of HRT in menopause attenuated HPA activity either in basal condition or in response to mild stress exposure. With regard to the CWT performance, all menopausal women took significantly longer than young women to perform the test. However, long-term HRT significantly reduced the number of errors made during the test. CONCLUSIONS: The present study suggested that long-term HRT could help menopausal patients to cope with mild stress and to improve mental performances.

Adrenal dysregulation in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a chronic progressive neuromuscular disorder of unknown etiology, characterized by weakness, muscle wasting, fasciculations and increased reflexes, with conserved intellect and higher function. The disease is due to degeneration of the motor neurons in the cerebral cortex, brainstem nuclei and anterior horns of the spinal cord. Although ALS poses an extreme burden on individual condition, data are missing concerning the regulation of adrenal function in the disease. In the present study we investigated cortisol levels in saliva of ALS patients as compared to healthy subjects. The results showed the loss of circadian rhythm of cortisol levels in ALS; in particular, levels of cortisol in the evening sample were significantly increased in ALS patients with respect to controls. Moreover, ALS patients did not show any physiological increase of cortisol levels following an unexpected mild stress (color-word Stroop test). These findings indicate the dysregulation of adrenal activity in the disease.

Altered circadian cortisol secretion in Alzheimer's disease: clinical and neuroradiological aspects.

We determined circadian salivary cortisol levels in 18 outpatients affected by probable Alzheimer's disease (AD) and looked for a possible correlation with both cognitive impairment and brain CT scan findings. The diagnosis of probable AD was made according to the NINCDS-ADRDA criteria. The severity of cognitive impairment was quantified using the Mini Mental State Examination (MMSE) and the Global Deterioration Scale (GDS). Cortisol levels were measured on saliva samples collected at 08:00 AM and 08:00 PM. For each sample, a duplicate cortisol measurement was performed on 50 microl of saliva by means of a modified commercial radioimmunoassay kit. At the same time, 11 of the 18 AD patients enrolled also underwent a brain CT scan to estimate cerebral atrophy by using linear indexes. The mean value of cortisol levels was significantly higher in AD patients than in controls at both the morning and the evening measurements, and the circadian fluctuation of cortisol was less marked in AD patients than in controls, although this difference did not reach statistical significance. Morning cortisol levels were significantly correlated to both the MMSE and the GDS scores. A significant correlation was also found between morning cortisol levels and all the cerebral atrophy indexes. By contrast, no correlation was observed between evening cortisol levels or cortisol circadian fluctuations and either cognitive impairment or cerebral atrophy. In conclusion, despite the potential biases deriving from the small sample and the limitations of the CT scan study, our results suggest that, in AD patients, hypercortisolemia is correlated with severity of the disease.

Behavioral sensitization to heroin by cannabinoid pretreatment in the rat.

The behavioral consequences of acute heroin challenge (0.5 mg/kg, s.c.) were measured in rats previously submitted to repeated administration of increasing doses of the synthetic cannabinoid receptor agonist, R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo-[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate (WIN55212.2) (first day 2 mg/kg, second day 4 mg/kg, third day 8 mg/kg) or vehicle. Heroin administration to rats pretreated with vehicle produced catalepsy. The same dose of heroin in WIN55212.2-pretreated rats was followed by a marked increase of locomotor activity with stereotyped and non-stereotyped behaviors. These effects were blocked by the opioid receptor antagonist, naloxone. These findings indicate that pretreatment with WIN55212.2 produces cross-sensitization to heroin in the rat. These changes might reflect long-lasting changes of receptor population or transcriptional mechanisms in the mesolimbic system.

Actual stress, psychopathology and salivary cortisol levels in the irritable bowel syndrome (IBS).

Although irritable bowel syndrome (IBS) can be considered a biopsychological disorder in which an association between life stress and physiological changes leading to bowel irregularity is present, there is a lack of data concerning possible modifications of the adrenal function during the disease. The aim of the present study was to measure biological and psychological variables related to the activity of the hypothalamo-pituitary-adrenal axis in IBS patients compared to healthy subjects. Cortisol was measured in the saliva (obtained by a stress-free, non invasive collection procedure) of 55 IBS outpatients and 28 matched controls. Moreover, each subject completed the following self-administered questionnaires: the Rome Burnout Inventory (RBI) in its physical (RBI-PE) and emotional-mental exhaustion (RBI-EME) components, Beck Depression Inventory, State and Trait Anxiety Inventory (STAI), Perceived Social Support Scale (PSSS) and a Scale for the Assessment of Perceived Actual Work-Non Work Stress. Compared with controls, IBS subjects showed significantly higher levels of cortisol in the morning and lower in the evening, while they maintained the physiological circadian fluctuation (i.e. cortisol morning level higher than in the evening). Moreover, IBS patients presented a significant difference from controls in RBI-PE scores, which confirms the presence of fatigue, a symptom frequently reported by the patients. Compared with controls, no differences were found in IBS patients with respect to other psychological parameters. These findings suggest a dysregulation of the adrenal activity in IBS patients. The results may be relevant considering that changes in cortisol levels have been shown to be sensitive indicators of psychosocial stress and coping patterns in both laboratory and life situations.

Behavioral sensitization to WIN55212.2 in rats pretreated with heroin.

There is evidence of similarities and interactions between central opioid and cannabinoid system with reference to drug reinforcement and abuse. Here we demonstrate that repeated injection of heroin produces behavioral sensitization towards administration of the synthetic cannabinoid receptor agonist WIN55212.2 in the rat. These effects were blocked by both the cannabinoid antagonist SR141716A and the opioid antagonist naloxone. These findings suggest that repeated exposure to heroin produces neuroadaptative changes in brain circuits that contribute to mediate the behavioral consequences of acute administration of WIN55212.2. The present results expand our knowledge on the interactions between central opioid and cannabinoid systems with respect to drug abuse.