The influence of childhood abuse on cortisol levels and the cortisol awakening response in depressed and nondepressed older adults

Objectives: Childhood abuse has been associated with depression in later life. This may be related to hypothalamic-pituitary-adrenal (HPA) axis functioning. Therefore we aimed to examine the impact of childhood abuse and its interaction with depression on cortisol levels in older adults.

Methods: Data from 418 participants (mean age 70.8 years) in the Netherlands Study of Depression in Older Persons (NESDO) were used; 187 participants experienced childhood abuse; 309 participants had a diagnosis of depression. Diurnal cortisol levels were determined using six saliva samples from every participant. Multiple regression analyses were performed.

Results: Significant negative associations between childhood abuse and morning cortisol levels were found. In nondepressed persons, both psychological and sexual abuse were associated with greater dynamics of the HPA axis in response to awakening.

Conclusions: Childhood abuse is associated with lower basal cortisol levels at awakening irrespective of major depressive disorder (MDD). Higher reactivity of the HPA axis during the hour after awakening was found in nondepressed participants only, which might suggest that late-life depression modifies the effect of childhood abuse on the HPA axis. Older adults with a history of childhood abuse may be more negatively affected by stress or stressful events and this is reflected in dysregulation of the HPA axis.     

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.     

Use of saliva cortisol in the dexamethasone suppression test

In a sample of 26 inpatients (15 primary endogenous depressives and a heterogeneous comparison group of 11 psychiatric patients), results of the dexamethasone suppression test (DST) for endogenous depression were compared when cortisol was measured in plasma (total and free) and in saliva. Results showed a close linear relationship among plasma total and free cortisol, plasma total cortisol, and saliva cortisol, and between free plasma and saliva cortisol. A saliva cortisol cutoff point of 70 ng/dl achieved the same sensitivity (67%), specificity (91%), and diagnostic confidence (91%) as the best cutoff scores of plasma total cortisol (5 μ/dl) and plasma free cortisol (0.15 μ/dl). These results suggest that saliva cortisol, which directly reflects the biologically active fraction of cortisol, can be used as a reliable and more practical index in the DST, especially in outpatients.     

Midwinter insomnia in the subarctic region: evening levels of serum melatonin and cortisol before and after treatment with bright artificial light

"Midwinter insomnia" (MI), mainly characterized by difficulties in falling asleep at night, is a common complaint during the period of obscuration or "dark period" north of the arctic circle. We hypothesize that MI is a result of a phase delay of the sleep-wake cycle due to insufficient exposure to daylight. In the present study based on this hypothesis, we wanted to find out whether otherwise healthy subjects with MI show abnormalities in the endocrine markers melatonin and cortisol late in the evening, and whether exposure to intensive light for one half hour in the morning for 5 days has any effect on the insomnia and on the endocrine variables. Nine subjects with typical MI were compared to eight controls. Before light exposure, the MI group had a significantly lower level of plasma melatonin in the evening than the controls, and a nonsignificant increase of plasma cortisol. After light exposure, the following results were seen in the MI group: sleep latency was moderately but significantly shortened, plasma melatonin increased to the same level as in the controls, and there was a nonsignificant increase of plasma cortisol. These results are largely in accordance with the predictions made from the phase delay hypothesis. However, other explanations cannot be ruled out.     

The effects of light therapy on depressed elders

BACKGROUND: Elderly depression has gradually become a severe issue in the health care system. No studies have focused on evaluating the effects of light therapy on the elderly with depression in a subtropical climate area. OBJECTIVES: To evaluate the effects of light therapy on hospitalized, depressed elders living in a subtropical climate area. METHODS: Experimental design was used. For the experimental group, patients sat in front of a light box, receiving 5000 lux in the morning. The light therapy course was administered for 50 minutes per day and lasted for 5 days. The control group did not receive any treatment. RESULTS: Depressive symptoms were significantly reduced in the experimental group at post-test but no significant decline was found in the control group. CONCLUSIONS: Based upon the results of this study, light therapy could be used to decrease depressive symptoms in the elderly.     

Influence of age on the cortisol response to dexamethasone

Controversy exists regarding the association of age with postdexamethasone serum cortisol levels. We evaluated this relationship in 95 patients with major depressive disorder and 49 healthy controls. Age and 8 a.m. postdexamethasone cortisol levels were not correlated among the healthy controls, but were positively associated among the depressives. There was also a trend for age and 4 p.m. postdexamethasone cortisol levels to be positively associated in depressives. Multiple linear regression analyses revealed that these associations could not be explained by other variables such as sex, psychotic features, or familial subtype of depression. Several hypotheses that might account for these associations are examined.     

Saliva cortisol and response to dexamethasone in children of depressed parents.

BACKGROUND: Major depression (MDD) is heritable, and children of depressed parents are at higher risk for the development of depression. However, depression in a parent might also act as a stressor leading to increased activation of neuroendocrine stress circuits. To address this question we examined saliva cortisol in children whose parents have a history of MDD. METHODS: We recruited 15 families with one parent with MDD (26 prepubertal children) and 16 control families without history of parental MDD (32 prepubertal children). All parents and children underwent Structured Clinical Interview for DSM-IV and Kiddie Schedule For Affective Disorders And Schizophrenia interviews, respectively. Families were asked to collect morning, afternoon, and bedtime saliva samples for 4 days for 2 weeks. At bedtime of the 3rd day, dexamethasone was administered. Two doses, standard and low, were used in each family. RESULTS: The majority of children demonstrated no psychiatric diagnosis. Children with MDD parents showed higher cortisol basally and higher cortisol after both 25 mg and 5 mg dexamethasone. However, this effect occurred predominantly in children whose parents were currently depressed. There were strong correlations for cortisol between parents and children (r = 52 in depressed; r = 499 in control). CONCLUSIONS: Elevated cortisol and impaired feedback seemed to reflect an environmental effect of MDD in a parent.     

The association of major depression, conduct disorder, and maternal overcontrol with a failure to show a cortisol buffered response in 4-month-old infants of teenage mothers.

BACKGROUND: Adolescent pregnancy can be associated with major depression (MD) and conduct disorder (CD). Some infants of adolescent mothers are prenatally exposed to these factors, which may result in heightened risk for perturbations of their stress systems. Between 2 and 4 months, a normal shift occurs in the adrenocortical system in which we observe a marked decrease in infant cortisol response when facing mild stressors. This study aimed to explore whether MD (lifetime, during pregnancy, postpartum), CD, and maternal overcontrol are associated with increased cortisol reactivity in 4-month-old infants of teenage mothers. METHODS: Using arm restraint as a stressor, morning salivary cortisol was taken prestressor and poststressor in 212 infants during a laboratory visit. Major depression and CD were measured with the computerized National Institute of Mental Health Diagnostic Interview Schedule (NIMH-DIS), postpartum depressive mood was measured with the Edinburgh Postnatal Depression Scale, and overcontrol was observed with the CARE-Index. RESULTS: Independent of the predictors, there was a dampened cortisol response. Infants of mothers with lifetime MD and of average to highly overcontrolling mothers showed increased cortisol reactivity. Conduct disorder and cortisol levels were not associated. CONCLUSIONS: Future studies should detect whether the absence of a dampened cortisol response in infants whose mothers have lifetime MD or display overcontrolling parenting is stable over time.     

Major depression in late life is associated with both hypo- and hypercortisolemia.

BACKGROUND: In younger adults, depression has been associated with hypercortisolemia. In older depressed patients, however, both low and high cortisol levels have been reported. We examined the possibility of a U-shaped association between depression and cortisol in older people, suggesting both hypo- and hyperactivity of the hypothalamic-pituitary-adrenal axis. We also examined whether this might represent different depression subtypes. METHODS: This population-based study included 1185 subjects aged 65 and older. Depression was measured at both diagnostic (major depression) and symptomatic (subthreshold depression) levels of caseness. Plasma concentrations of cortisol (CORT) and corticosteroid binding globulin (CBG) were determined. From these (CORT/CBG), a free cortisol index (FCI) was computed. RESULTS: The association between cortisol and major depression was U-shaped (B CORT = -9.50 [SE 3.85] p = .014; B CORT(2) = .008 [SE .003] p = .021). Hypocortisolemic depression (lower cortisol tertile) was associated with female sex, joint diseases, and smoking. Hypercortisolemic (upper cortisol tertile) depression was associated with older age, male sex, cardiovascular diseases, nonsteroidal antiinflammatory use, and (borderline significant) cognitive impairment. CONCLUSIONS: In older people, the association between cortisol and major depression is U-shaped. Hypo- and hypercortisolemic depression may represent different depression subtypes, requiring different clinical management.     

Clinical burnout is not reflected in the cortisol awakening response, the day-curve or the response to a low-dose dexamethasone suppression test

Burnout is presumed to be the result of chronic stress, and chronic stress is known to affect the HPA-axis. To date, studies on HPA-axis functioning in burnout have showed inconsistent results. In the present study, a large sample (n=74) of clinically diagnosed burnout individuals, mostly on sick-leave, were included and compared with 35 healthy controls. Salivary cortisol was sampled on 2 days to determine the cortisol awakening response (CAR) and the day-curve. In addition, the dexamethasone suppression test (DST) was applied to assess the feedback efficacy of the HPA-axis. There were no differences observed in the CAR, day-curve or CAR after DST in the burnout group as compared to a healthy control group. Burnout shows overlap in symptoms with chronic fatigue syndrome (CFS) and depression. Therefore, differential changes in HPA-axis functioning that resemble the hypo-functioning of the HPA-axis in CFS, or rather the hyper-functioning of the HPA-axis in depression, might have obscured the findings. However, no effect of fatigue or depressive mood on HPA-axis functioning was found in the burnout group. We concluded that HPA-axis functioning in clinically diagnosed burnout participants as tested in the present study, seems to be normal.     

The cortisol awakening response in amyotrophic lateral sclerosis is blunted and correlates with clinical status and depressive mood

Considerable evidence indicates that amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease of the motor system, has an enormous impact on the patient's emotional and physical well-being. As previous findings indicated that particularly the rise in cortisol levels immediately after awakening, i.e., the cortisol awakening response (CAR), is associated with indices of physical and emotional well-being, we compared the CAR of 29 admitted ALS patients with that of 12 age-matched caregiver controls. Saliva samples for cortisol measurement were collected immediately, 15, 30 and 45 min after awakening. The severity of ALS progression was quantified using the ALS functional rating scale (ALSFRS) and manual muscle test (MMT). Depressive mood status in ALS patients was determined with the Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS). Salivary cortisol levels of ALS patients did not differ from those of caregiver controls at awakening, 15 min or 45 min after awakening, but were significantly lower at 30 min after awakening. Area under the curve analysis confirmed that the CAR was significantly smaller in ALS patients than in caregiver controls. A smaller CAR in ALS patients was significantly correlated to poorer clinical status, as assessed with both the ALSFRS and MMT rating instruments. Further, a smaller CAR significantly correlated with a more severe depressive mood status. No correlations were observed between total cortisol output during the first 45 min post-awakening and clinical or depressive status. In conclusion, our findings indicate that ALS patients show a blunted CAR, correlated with disease and depression severity.     

Lithium augmentation increases post-dexamethasone cortisol in the dexamethasone suppression test in unipolar major depression

Although considerable evidence exists on the efficacy of lithium as an augmenting agent in refractory depression, the underlying neurobiology of this phenomenon is unknown. In patients with major depression, changes of the hypothalamic-pituitary-adrenocortical (HPA) system have been detected by means of the dexamethasone suppression test (DST), when administered during treatment with tricyclic antidepressants. We investigated whether the DST also reveals alterations of the HPA system during lithium augmentation. We also sought to identify whether response to lithium augmentation can be predicted with the DST. Twenty-five patients with unipolar major depression, who did not respond to an adequate antidepressant monotherapy of at least 4 weeks, were measured for basal (pre-dexamethasone, 0800h) cortisol and ACTH levels and were administered the DST the day before initiation of lithium augmentation treatment. The same neuroendocrine procedures were repeated after 3 to 4 weeks. Criteria of response to lithium augmentation, defined as a reduction of the Hamilton Depression Rating Scale (HDRS17) score by > or =50% and an end point score of 9 or less, were determined by weekly HDRS ratings. The DST revealed a statistically significant increase of the post-dexamethasone cortisol values (P = 0.021) and an increase in the post-dexamethasone ACTH values (P = 0.051) during lithium augmentation as compared to pre-treatment baseline evaluations. The pre-dexamethasone hormone values were unchanged. The number of non-suppressors at baseline was one and increased to three at follow-up. Results of DST did not predict response to lithium augmentation, which occurred in 40% of subjects. Results suggest that lithium augmentation increases HPA system activity, as indicated by the increase of post-dexamethasone cortisol and ACTH levels measured by the DST. This is in contrast to the established decline of HPA system activity during treatment with tricyclic antidepressants.     

The effect of amphetamine on plasma cortisol in patients with endogenous and non-endogenous depression

Amphetamine sulphate (0.1 mg/kg, i.v.) produced no consistent change in plasma cortisol levels in 21 depressed patients. Seven patients with endogenous depression (melancholia) were matched with seven patients with non-endogenous depression; there was no difference in the cortisol response to amphetamine between these two groups.     

Morning bright light therapy for sleep and behavior disorders in elderly patients with dementia

Fourteen inpatients with dementia showing sleep and behavior disorders (average age = 75 years), and 10 control elderly people (average age = 75 years) were carefully observed for 2 months. Four weeks of morning light therapy markedly improved sleep and behavior disorders in the dementia group. The measurement of sleep time and the serum melatonin values suggests that sleep and behavior disorders in the dementia group are related to decreases in the amplitude of the sleep-wake rhythm and decreases in the levels of melatonin secretions. Morning light therapy significantly increased total and nocturnal sleep time and significantly decreased daytime sleep time. These results indicate that morning bright light is a powerful synchronizer that can normalize disturbed sleep and substantially reduce the frequency of behavior disorders in elderly people with dementia.     

Correcting delayed circadian phase with bright light therapy predicts improvement in ADHD symptoms: A pilot study

Attention-deficit/hyperactivity disorder (ADHD) is a common condition with comorbid insomnia reported in >70% of children and adults. These patients demonstrate delays in sleep-wake rhythms, nocturnal rise in melatonin, and early morning rise in cortisol. Given that standard psychopharmacologic treatments for ADHD often do not completely control symptoms in participants with circadian rhythm delay, we sought to test whether bright light therapy (BLT) advances circadian rhythms and further reduces ADHD symptoms over standard treatments. In addition to standard of care, participants with ADHD diagnosis underwent 1 week of baseline assessment followed by 2-weeks of 30-min morning 10,000-lux BLT beginning 3 h after mid-sleep time. Participants minimized overhead light after 4 p.m., wore an actigraphy watch, and recorded BLT time on daily sleep logs. Dim Light Melatonin Onset (DLMO) was assessed at baseline and after 2-week treatment. ADHD symptoms were measured by the ADHD-Rating Scales (ADHD-RS). BLT significantly advanced the phase of DLMO by 31 min [mean time (SEM), 20:36 (0:21) advanced to 20:05 (0:20)] and mid-sleep time by 57 min [4:37 (0:22) advanced to 3:40 (0:16); paired t-tests, p = 0.002 and 0.004, respectively). Phase advances (in DLMO or mid-sleep time) were significantly correlated with decreased ADHD-RS total scores (p = 0.027 and 0.044) and Hyperactive-Impulsive sub-scores (p = 0.014 and 0.013, respectively). Actigraphy analysis for a subset of 8 participants with significant DLMO phase advance revealed no significant changes in total sleep time, sleep efficiency, wake after sleep onset, or percent wake during sleep interval. This is the first successful use of BLT for advancing melatonin phase and improving ADHD symptoms in adults. BLT may be a complementary treatment for both delayed sleep timing and ADHD symptoms in adults.     

The effect of depression, anxiety and early life trauma on the cortisol awakening response during pregnancy: preliminary results

The purpose of this study was to examine the effects of maternal depression and anxiety on the cortisol awakening response (CAR), a marker of the hypothalamic-pituitary-adrenal (HPA) axis function, during pregnancy. Sixty-six pregnant women were studied between 25 and 33 weeks of gestation and were identified as either Depressed (n=33) or healthy, Control (n=33), based on depression scores and lifetime psychiatric history. Saliva samples were collected (passive drool) upon awakening and at +30 and +60 min thereafter. The CAR was not significantly different between women who were depressed during pregnancy compared to healthy control women. However, women taking antidepressant (AD) medication showed an attenuated CAR (time x AD use interaction, p=0.06). Childhood maltreatment (as measured with the Childhood Trauma Questionnaire) was associated with a lower baseline cortisol concentration explaining 12% of the variance, controlling for wake-up time and AD use. There is a complex interplay of factors involved in the HPA axis regulation of vulnerable women during pregnancy, including depression, anxiety, early life stress and psychotropic medication use, which remain unclear. The CAR may provide important information about the maternal HPA axis during pregnancy and warrants further investigation in larger cohorts.