Chronotype and diurnal cortisol profile in working women: differences between work and leisure days

The influence of chronotype on the diurnal profile of salivary cortisol was examined in a sample of 187 healthy women: 21 evening chronotype, 24 morning chronotype and 142 intermediate chronotype. Saliva samples were collected at waking, 30 min post-awakening, at 1000 h, 1200 h, 1500 h, 1700 h and at bedtime on one work and one leisure day. Several components of the diurnal profile were examined including the cortisol awakening response, the total cortisol output and the diurnal profile on both the work and the leisure day, a significant main effect of time emerged (both p<0.01). After adjustment for age, smoking status, self-rated health, time of waking, and sleep problems, no effect of chronotype was evident for cortisol in the evening, the cortisol awakening response, or total cortisol output over the working day. However, on the leisure day, total cortisol output was greater in evening-types than intermediate or morning-types, after adjustment for covariates (p=0.029). The present data indicate that chronotype has a limited impact on the diurnal cortisol profile of healthy women, and may be somewhat impervious to individual preferences for morning or evening activity.     

Effects of naloxone-HCl on cortisol levels in patients with affective disorder and normal controls

Cortisol levels were measured before and after administration of naloxone-HCl in patients with affective disorder (n = 16) and normal control subjects (n = 8). On two consecutive days, 20 mg of naloxone-HCl or placebo was administered i.v. over 15 minutes in a double-blind crossover design. Blood samples were collected at 30, 15, and l minute(s) both before and after infusion. Cortisol rose from a mean baseline level of 14.8 microgram% to a mean peak level of 23.1 microgram% following the naloxone administration. Significant cortisol increases were found in both the 15- and 30-minute samples during the naloxone session. There were no differences between patient and normal subject samples or between diagnostic groups. A subgroup of manic patients who had responded to naloxone with a reduction of their manic behavior also had an attenuated cortisol response to naloxone. This proved to be an artifact secondary to variability in the cortisol response in these patients.     

Decreased cortisol response to awakening is associated with cognitive vulnerability to depression in a nonclinical sample of young adults

Due to its high intraindividual stability, the cortisol awakening response (CAR) may be regarded as a trait measure of the dynamics of the HPA-axis activity. The present study aimed at investigating associations of the CAR with rumination as a cognitive vulnerability marker for depression assessed by both a trait measure and by experimental manipulation. After induction of sad mood by viewing a sad sequence of a movie, 42 healthy university students were randomly induced to either ruminatively self-focus on their feelings or to distract themselves from their mood by concentrating on respective text cards for 8min. Trait rumination and distraction were measured by the Response Styles Questionnaire (RSQ) at baseline (T0), while current mood was recorded before (T1) and after (T2) the mood induction as well as after the rumination/distraction induction (T3) using the Positive and Negative Affect Schedule (PANAS). Basal saliva cortisol levels were measured independently on a different day. After mood induction, levels of mood were lowered significantly. Participants subsequently induced to ruminate kept their negative mood whereas participants induced to distract themselves showed a reduction in negative mood. Self-focused trait rumination amplified low mood in both induction conditions. A decreased CAR was associated with self-focused rumination and with less improvement of sad mood after induced distraction. We conclude that the two variables apparently share specific vulnerability qualities towards depression by hampering the adaptive shift of attention to external cues during dysphoric moods, probably involving lowered disinhibition of task-irrelevant negative emotional processing. The present study provided first indications of a possible relationship between a cognitive vulnerability marker for depression and characteristics of basal neuroendocrine activity regarding their association with the course of experimentally induced dysphoric mood.     

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.     

Diurnal patterns of salivary cortisol across the adolescent period in healthy females

When examining the diurnal profile of the hormone cortisol in children and adolescents developmental issues are particularly relevant. Previous findings regarding relationships between cortisol secretory activity and reproductive (pubertal) maturation lack clarity and may reflect methodological inconsistencies between studies. This study examined the diurnal cortisol profile across female adolescence, with a particular focus on an obvious and unique marker of development: menarche. In a cross-sectional design, 61 healthy female adolescents aged 9-18 years (mean age 13.89 years, S.D.+/-2.72) collected eight saliva samples per day on two consecutive weekdays. Samples were collected at awakening, 15, 30 and 45min and 3, 6, 9 and 12h post-awakening in order to capture both the cortisol awakening response (CAR) and the subsequent period of decline. Demographic information was recorded and participants also completed the Spielberger State-Trait Anxiety Inventory. Patterns of cortisol secretion exhibited good intra-individual stability across the two sampling days. Participants evidenced a robust diurnal pattern, with cortisol levels peaking approximately 30-45min post-awakening (the CAR) and steadily declining concentrations over the remainder of the day. Differences according to developmental status (in terms of whether or not participants had experienced first menses: menarche) were observed in the time of peak secretion of the CAR, and these distinct patterns could not be accounted for by group differences in demographic, situational or psychological characteristics measured in this study. This effect for the CAR was associated with the onset of menarche alone, unlike cortisol levels over the remainder of the day. For those who had undergone menarche, were older and of greater BMI, cortisol levels remained higher over the day. There was a significant difference in cortisol concentrations at 6h post-awakening between pre- and post-menarche groups. Again, these differences in daytime cortisol secretory activity could not be attributed to situational or psychological factors. Establishing patterns of cortisol secretion in healthy female adolescents provides an important baseline from which to investigate hypothalamic-pituitary-adrenal (HPA) physiology, measured via salivary cortisol, in adolescent populations with known or suspected psychopathology.     

Psychological coping styles and cortisol over the day in healthy older adults

Patterns of psychological coping are associated with a variety of health outcomes but the underlying pathways are not yet established. The purpose of this study was to assess the relationship between salivary cortisol output over the course of a day and coping style. Data were available from 350 men and 192 women with an average age of 60.9 years. Participants were drawn from the Whitehall II cohort, and had no history of cardiovascular disease. Individuals who were taking medication that might affect cortisol levels were also excluded. Saliva samples were provided on waking, then 0.5, 2.5, 8 and 12 h after waking, and just before the participant went to sleep. Coping style was measured with a standard instrument, the COPE, and data were factor analysed to generate three factors: seeking social support, problem engagement and problem avoidance. The relationships between these factors and the cortisol awakening response (CAR), the slope of cortisol change over the day and total cortisol output over the day (excluding the waking period) were assessed using multiple linear regression. Cortisol output over the day was inversely associated with coping with stress by seeking social support (p=0.034) and by problem engagement (p=0.003), independently of age, gender, body mass index, smoking, depression, self-rated health, time of waking and income. Individuals who coped by problem engagement and seeking support had lower cortisol levels. Additionally, gender, BMI, smoking, self-rated health and time of waking were independently related to cortisol output over the day. There were no significant associations between coping and the CAR or cortisol slope over the day. The results indicate that adaptive coping styles are related to low levels of cortisol over the day, suggesting that neuroendocrine pathways may partly mediate relationships between psychological coping and health.     

Association between seasonal affective disorder and subjective quality of the sleep/wake cycle in adolescents

The relationship between seasonal affective disorder (SAD) and subjective quality of sleep/wake cycle in adolescents was explored. The Seasonal Pattern Assessment Questionnaire for Children and Adolescents (SPAQ-CA) and Mini Sleep Questionnaire (MSQ) were administered to 345 adolescents living in the city of Cesena (Emilia-Romagna region, Italy) (299 females; age range: 14–18 years), to determine SAD and perceived quality of the sleep/wake cycle. The response rate was 92% for females and 90.2% for males. The MSQ includes two factors, sleep and wake, with lower scores corresponding to a lower quality of sleep and wake. The MSQ includes cut-off criteria to detect a good or bad sleep and wake quality. Adolescents with SAD (16±5.7) scored significantly lower than those not affected on wake factor (19.5±4.3), while no effect has been observed on sleep factor. SAD was the only one significant predictor of good/bad wake quality, while it did not reach significant level with reference to good/bad sleep quality. Present results are indications of a possible influence of SAD on wake quality and further studies are necessary to confirm them.     

Ageing, physical function, and the diurnal rhythms of cortisol and dehydroepiandrosterone

The present study examined the relationship between ageing, physical function and the diurnal rhythms of cortisol and dehydroepiandrosterone (DHEA). Participants were 36 community dwelling older adults aged between 65 and 86 years old. Salivary cortisol and DHEA were measured over the course of one day: immediately upon awakening, 30 min later, and then 3 h, 6 h, 9 h and 12 h post-awakening. Participants completed the Nottingham extended activities of daily living index, the Berg Balance Scale and their handgrip strength was assessed. Older participants had a significantly higher cortisol area under the curve (AUC), lower overall DHEA levels, lower DHEA AUC, a decreased diurnal slope of decline and increased cortisol:DHEA ratio. Lower diurnal cortisol levels were associated with poorer performance on the Berg Balance Scale and lower handgrip strength, and those with a flattened DHEA diurnal profile reported less independence in carrying out daily tasks. These associations withstood adjustment for age. In conclusion, this study suggests an association between cortisol, DHEA, ageing and physical function.     

Actigraphy in patients with seasonal affective disorder and healthy control subjects treated with light therapy.

BACKGROUND: Abnormalities of the circadian rest-activity cycle are hypothesized to accompany the clinical picture of seasonal affective disorder (SAD). The purpose of this study was to investigate if bright light therapy (BLT) is able to reverse these disturbances. METHODS: Seventeen SAD outpatients and 17 sex- and age-matched healthy control subjects were treated with BLT administered in the morning for 4 weeks. Activity levels were measured with wrist actigraphy. RESULTS: SAD patients had 33% lower total (p = .031) and 43% lower daylight activity (p = .006) in week 1 compared with control subjects. The relative amplitude of the sleep-wake cycle was attenuated by 6% in patients (p = .025); they were phase delayed by 55 minutes (p = .023) and had significantly lower sleep efficiency (p = .030). Total (p = .002) and daylight activity (p = .001) increased after 4 weeks of treatment in SAD patients. Moreover, BLT led to increase of relative amplitude (p = .005), advance of delayed rhythms (p = .036), and improved sleep efficiency (p = .011) in patients. Intradaily stability, measuring the strength of coupling of the rhythm to external zeitgebers, increased by 9% both in patients and healthy control subjects (p = .032). CONCLUSIONS: Treatment with BLT normalizes disturbed activity patterns and restores circadian rhythms in SAD patients. BLT might also stabilize the circadian rhythm in nondepressed individuals during the fall-winter season.     

Post-traumatic disorder symptoms and blunted diurnal cortisol production in partners of prostate cancer patients

Prostate cancer (PC) is the most common cancer diagnosed in men, and research suggests that coping with this illness can cause significant distress in patients as well as their partners. This study examined the relationship of caregiving for a partner with PC with diurnal cortisol output in women between the ages of 42 and 75 years old. Participants were women whose partners had PC (n = 19) and women who were in relationships with men with no diagnosed medical illness (n = 26). Women provided saliva samples (4 times per day over 3 days) in their natural environment. The Structured Clinical Interview for DSM-IV Axis-I Disorders was also conducted to assess for the presence of post-traumatic stress disorder (PTSD) and major depression. Partners of men with PC had lower daily cortisol output across the three days than controls, F(1,444.08) = 20.72, p<.001). They were also more likely to report PTSD symptoms with 68.4% of PC partners fulfilling criteria for sub-threshold PTSD as compared to 23.1% of controls (χ(2) = 11.30, p = .01). Mixed model analyses revealed that the presence of sub-threshold PTSD symptoms significantly predicted cortisol production, F(1,419.64) = 5.10, p<.01). Regardless of caregiver status, women who reported at least sub-threshold PTSD symptoms had lower cortisol production than those with no PTSD symptoms. Major depression did not explain differences in cortisol production between partners of PC patients and controls. Although these findings are preliminary, they highlight the importance of developing interventions aimed at reducing risk of psychopathology in partners of men with PC.     

Therapeutic effects of escitalopram and reboxetine in seasonal affective disorder: A pooled analysis

The monoaminergic neurotransmitters serotonin and noradrenaline have both been implicated in the pathogenesis of seasonal affective disorder (SAD). However, the differential therapeutic value of selective serotonin reuptake inhibitors (SSRI) and selective noradrenaline reuptake inhibitors (NARI) in SAD has not been assessed until now. This study compares data from two open-label trials with similar methodology investigating the SSRI escitalopram and the NARI reboxetine. 20 SAD patients were treated with escitalopram (10-20 mg) and 15 patients received treatment with reboxetine (fixed dosage: 8 mg) over 6 weeks. Ratings included the structured interview guide for the Hamilton depression rating scale, SAD version (SIGH-SAD), the clinical global impression of severity (CGI-S) and improvement (CGI-I) and the UKU side effect rating scale. Treatment led to a significant reduction in SIGH-SAD score, CGI-S and CGI-I after one week in the reboxetine group and after two weeks in the escitalopram group. SIGH-SAD score was significantly lower in the reboxetine group at weeks 1, 2 and 4 but not at the end of the study. The response rate (SIGH-SAD <50% of baseline value) and the remission rate (SIGH-SAD <8) were not significantly different after 6 weeks of treatment, but the time to response and to remission was significantly shorter in the reboxetine group. The number and severity of side effects were higher in patients treated with reboxetine at all time points. Thus escitalopram and reboxetine were equally effective in treating SAD on all primary and secondary outcome measures. Reboxetine displayed a faster onset of action, but was associated with more pronounced side effects. Further studies comparing SSRI and NARI in SAD are warranted.     

Effects of tryptophan depletion and catecholamine depletion on immune parameters in patients with seasonal affective disorder in remission with light therapy.

BACKGROUND: Altered immunologic parameters are found in symptomatic depressed patients relative to remitted depressed patients and healthy controls. We investigated whether tryptophan depletion and catecholamine depletion induce alterations in immunologic parameters in patients with seasonal affective disorder remitted on light therapy, and whether these changes are associated with changes in mood. METHODS: Remitted patients with seasonal affective disorder underwent tryptophan depletion, catecholamine depletion, and sham depletion in a prospective randomized, double-blind crossover design. Measures of depression, plasma levels of tryptophan and catecholamine metabolites, and plasma levels of cytokines (sIL-4, IL-6, neopterin, sTNF-R1 and sTNF-R2) were obtained at baseline, and 7, 24, and 30 hours after monoamine depletion. RESULTS: Tryptophan depletion decreased plasma total and free tryptophan levels; catecholamine depletion decreased plasma 3-methoxy-4-hydroxyphenylethyleneglycol and homovanillic acid levels. Tryptophan depletion and catecholamine depletion, but not sham depletion, induced a transient exacerbation of depressive symptoms (p <.001); plasma neopterin levels increased during tryptophan depletion and catecholamine depletion (p <.05). Tryptophan depletion and catecholamine depletion induced a transient reduction of plasma sIL-4 levels (p <.05). A significant correlation was found between sIL-4R levels and depression ratings after tryptophan depletion (r = -.61, p <.05). CONCLUSIONS: The monoamine depletion-induced alterations of humoral and cellular immunity suggest a potential role of immunologic parameters in the pathophysiology of seasonal affective disorder; however, the results must be considered preliminary and require further study.