Associations of salivary cortisol levels with inflammatory markers: the Multi-Ethnic Study of Atherosclerosis

Socioeconomic and psychosocial factors have been found to be associated with systemic inflammation. Although stress is often proposed as a contributor to these associations, no population studies have investigated the links between inflammation and biomarkers of stress. The current study examines associations between daily cortisol profiles and inflammatory markers interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor (TNF-a) in a population-based sample of 869 adults with repeat measures of cortisol over multiple days. Persons with higher levels of IL-6 had a less pronounced cortisol awakening response, a less steep daily decline, and higher cortisol area under the curve for the day with associations persisting after controls for risk factors and other cytokines. Persons with higher levels of TNF-a had lower cortisol levels upon waking, and flatter daily decline, although associations with decline were attenuated when controlling for inflammatory risk factors. Higher levels of IL-10 were associated with marginally flatter daily cortisol decline (p<.10). This study is the first to identify associations of basal cortisol activity and inflammatory markers in a population based sample. Findings are consistent with the possibility that HPA axis activity may mediate associations between psychosocial stressors and inflammatory processes. Additional prospective data are necessary to clarify the directionality of associations between cortisol and inflammatory markers.     

Stress in pregnancy and infant HPA axis function: conceptual and methodological issues relating to the use of salivary cortisol as an outcome measure

Problems regulating behaviour and emotions in infancy may be a risk factor for the development of psychopathology later in life. Compelling evidence from animal models suggests that one potential pathway to early dysregulation is fetal programming of the hypothalamic-pituitary-adrenal (HPA) axis. According to this model, prenatal maternal stress and anxiety during sensitive periods of development can lead to enduring changes in fetal and offspring neurodevelopment and behaviour. While there is emerging evidence from human studies to suggest a link between maternal negative mood states in pregnancy and various cognitive, behavioural, and emotional disturbances in offspring, it is not yet clear whether the programming mechanism demonstrated in animal studies also applies to humans. Few studies have directly assessed HPA axis function in the infants of prenatally stressed women. Research in this area has been constrained by a number of measurement challenges unique to the assessment of cortisol in infants. This paper discusses these challenges with a view to stimulating further research in the area.     

Persistence of abnormal cortisol levels in elderly persons after recovery from major depression

Background

Cortisol hypersecretion is characteristic of acute clinical depression, but little is known in fully recovered, non-treated elderly persons with a lifetime history of depression. This study was designed to examine patterns of diurnal cycle of cortisol in an elderly cohort without current depression or treatment for depression according to whether the person has or has not experienced a previous episode of depression or co-morbid depression with anxiety.

Methods

Cortisol secretion was evaluated in 162 community-dwelling elderly on a stressful and a non-stressful day (basal level). Past depression and anxiety disorders were assessed using a standardized psychiatric examination based on DSM-IV criteria (the Mini International Neuropsychiatric Interview).

Results

Antidepressant-free persons with a history of non-co-morbid major depression (6.8% of the sample) showed basal cortisol hypersecretion compared to those with depression and anxiety (8.6%) or controls. Several hours after exposure to a stressful situation, controls showed a sustained increase in cortisol secretion, which was not observed in persons with a history of depression. Persons with a history of depression with anxiety showed a similar cortisol secretion at baseline to controls but a heightened response to stressful situation; a pattern comparable to that observed in subjects with pure anxiety disorders (16.7%).

Conclusion

An abnormal HPA response persists even after effective treatment for depression. A history of co-morbid depression and anxiety gives rise to changes characteristic of anxiety alone. Our findings suggest that cortisol abnormalities may be trait markers for vulnerability to depression and for the differentiation of depression and depression with co-morbid anxiety.     

Anxiety disorders and comorbid depression in community dwelling older adults

Anxiety disorder is a common psychiatric problem during late‐life, and frequently co‐occurs with depression. High comorbidity between anxiety and depression may partly be explained by the definition of the disorders and the assessment of both disorders with one instrument at the same time. The current study investigates the relation of current and past depression with anxiety disorders in the Rotterdam Study, a large population‐based cohort study of older adults in the Netherlands (n study population = 5565). DSM‐IV anxiety disorder was ascertained with the Munich version of the Composite International Diagnostic Interview. DSM‐IV depression was diagnosed with the Schedules for Clinical Assessment of Neuropsychiatry (SCAN) on a different day. Past depression was assessed from general practitioners' records, self‐report, and a prior SCAN interview. Of the 457 persons with an anxiety disorder, 11.6% had a comorbid major depression, and another 6.3% had other depressive syndromes. However, 49.3% of persons with an anxiety disorder experienced or had in the past experienced a depressive episode. Our study suggests that comorbid depression in older adults with anxiety disorders may be less prevalent than previously suggested. However, the relation of current anxiety disorders with past depression is substantial. Copyright © 2011 John Wiley & Sons, Ltd.     

Diurnal salivary cortisol in pediatric posttraumatic stress disorder.

BACKGROUND: The hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathophysiology of posttraumatic stress disorder (PTSD). Additional information on basal cortisol levels in children exposed to trauma and experiencing PTSD symptoms may contribute to the understanding of the role of this axis in PTSD. METHODS: Fifty-one children (30 boys and 21 girls, mean age 10.7 years) with a history of exposure to trauma and PTSD symptoms were compared with 31 age- and gender-matched healthy control subjects. Salivary cortisol was obtained from participants during home measurements and was collected four times a day (prebreakfast, prelunch, predinner, and prebed) for up to 3 consecutive days. RESULTS: The clinical group demonstrated significantly elevated cortisol levels when compared with the control group. In addition, exploratory analyses revealed that girls with PTSD symptoms had significantly elevated cortisol levels when compared with boys with PTSD symptoms. CONCLUSIONS: The physiologic response of children with history of trauma and with PTSD symptoms may be characterized by heightened adrenal activity.     

Increased nocturnal secretion of ACTH and cortisol in obsessive compulsive disorder

Information on the function of the hypothalamic-pituitary-adrenal (HPA) axis, the main mammalian system of stress response, in obsessive compulsive disorder (OCD) is inconsistent. In this study, nine inpatients with a DSM-IV diagnosis of OCD without comorbid major depression (Yale-Brown Obsessive Compulsive Scale [Y-BOCS] score >15; HAMD-21 total score 16) and nine healthy matched controls were included. Blood of patients (seven males; 31.8 +/- 9.3 years, Y-BOCS: 27.3 +/- 4.3, HAMD-21: 13.3 +/-1.9) and controls (seven males, 31.6 +/- 9.1 years) was drawn every 20 min between 23:00 and 7:00 h during sleep using a long catheter for later ACTH and cortisol analysis. Secretion patterns of cortisol and ACTH were similar in both groups, in OCD, however, at a higher level. Area under the curve plasma concentrations of both ACTH (p<0.05) and cortisol (p<0.005) were significantly greater in patients with OCD (ACTH: 674.3 +/- 57.4; cortisol: 2148.4 +/-271.7) than in controls (ACTH: 460.2 +/- 61.0; cortisol: 1191.2 +/- 124.1). In conclusion, our findings suggest that the activity of the HPA axis in patients with OCD is increased compared to healthy controls.     

Schema therapy for personality disorders in older adults: a multiple-baseline study

Objective: No studies have been conducted yet into the effectiveness of treatment of personality disorders in later life. This study is a first test of the effectiveness of schema therapy for personality disorders in older adults.

Method: Multiple-baseline design with eight cluster C personality disorder patients, with a mean age of 69. After a baseline phase with random length, schema therapy was given during the first year, followed by follow-up sessions during six months. Participants weekly rated the credibility of dysfunctional core beliefs. Symptomatic distress, early maladaptive schemas, quality of life and target complaints were assessed every six months and personality disorder diagnosis was assessed before baseline and after follow-up. Data were analyzed with mixed regression analyses.

Results: Results revealed significant linear trends during treatment phases, but not during baseline and follow-up. The scores during follow-up remained stable and were significantly lower compared to baseline, with high effect sizes. Seven participants remitted from their personality disorder diagnosis.

Conclusion: Schema therapy appears an effective treatment for cluster C personality disorders in older adults. This finding is highly innovative as this is the first study exploring the effectiveness of psychotherapy, in this case schema therapy, for personality disorders in older adults.     

Association of cortisol with neuropsychological assessment in older adults with generalized anxiety disorder

Objectives: Older adults with generalized anxiety disorder (GAD) have elevated diurnal cortisol patterns and show an increased cortisol stress response, which may increase risk for cognitive dysfunction. The current secondary data analysis examined how neuropsychological assessment as a possible laboratory stressor affects cortisol levels in late-life GAD and, in turn, how cortisol levels affect cognitive performance.

Methods: The current sample consisted of 69 individuals with late-life GAD and 39 psychiatrically healthy group-matched comparison participants. Cognitive performance was measured with a neuropsychological battery and salivary cortisol was collected at several time points. Hierarchical regressions were performed to assess the moderating role of cortisol in the relationship between GAD status and cognitive performance.

Results: The results revealed that older adults with GAD showed significantly lower cortisol levels during neuropsychological assessment, compared to their baseline levels. Further, there was a significant interaction between post-neuropsychological assessment cortisol levels and GAD status on several measures of cognitive performance. The interaction indicated that there is a significant negative relationship between cortisol level and cognitive performance in the GAD participants and no such relationship in the comparison participants.

Conclusions: Our results revealed that participating in a neuropsychological assessment was associated with reduced cortisol in GAD participants, suggesting that refocusing attention such as engaging in cognitive tasks had a cortisol-lowering effect. Further, a higher cortisol level appears to have a detrimental effect on cognitive performance for individuals with GAD, but not psychiatrically healthy comparison participants. The methodological and treatment implications of these findings are discussed.     

Longitudinal course of salivary cortisol in post-traumatic stress disorder

OBJECTIVE: In chronic post-traumatic stress disorder (PTSD) lowered cortisol secretion and hypersuppression to dexamethasone has been described repeatedly. However, so far no longitudinal data on the natural course or on the effect of therapy are available. METHOD: We measured basal and post-dexamethasone morning salivary cortisol in a drug-free patient with chronic PTSD (DSM-IV) monthly for nearly 2 years and assessed PTSD and depressive symptoms. RESULTS: Salivary cortisol decreased dramatically 3 months after the traumatic event and in the further course showed an inverse relation to fluctuating but gradually improving PTSD symptoms. Post-dexa-methasone cortisol was suppressed below the detection limit early after trauma and rose again more than 1 year post-trauma. CONCLUSION: Both the potential renormalization of low cortisol levels in improving chronic PTSD and the putative vulnerability to develop PTSD in subjects with increased dexamethasone suppression need further research.     

Cross-sectional and 35-year longitudinal assessment of salivary cortisol and cognitive functioning: the Vietnam Era twin study of aging

High levels of cortisol, a sign of potential hypothalamic-pituitary-adrenal (HPA) axis dysregulation, have been associated with poor cognitive outcomes in older adults. Most cortisol research has focused on hippocampal-related abilities such as episodic memory; however, the presence of glucocorticoid receptors in the human prefrontal cortex suggests that cortisol regulation is likely to be associated with prefrontally-mediated executive function abilities. We hypothesized that elevated cortisol levels would be associated with poorer frontal-executive function in addition to episodic memory. We assessed cortisol from 15 saliva samples paralleling individual diurnal rhythms across three non-consecutive days in a group of 778 middle-aged twin men ages 51-60. Cognitive domains created from 24 standard measures included: general cognitive ability, verbal and visual-spatial ability, verbal and visual-spatial memory, short-term/immediate memory, working memory, executive function, verbal fluency, abstract reasoning, and psychomotor processing speed. Adjusting for general cognitive ability at age 20, age, race, and multiple health and lifestyle indicators, higher levels of average area-under-the-curve cortisol output across three days were significantly associated with poorer performance in three domains: executive (primarily set-shifting) measures, processing speed, and visual-spatial memory. In a 35-year longitudinal component of the study, we also found that general cognitive ability at age 20 was a significant predictor of midlife cortisol levels. These results possibly support the notion that glucocorticoid exposure is associated with cognitive functions that are mediated by frontal-striatal systems, and is not specific to hippocampal-dependent memory. The results also suggest that the direction of effect is complex.     

Emotional stress,cortisol response,and cortisol rhythm in autism spectrum disorders: A systematic review

BackgroundThis systematic review evaluated whether there is evidence for (i) increased emotional stress levels, and (ii) a different biological stress response or rhythm [i.e., cortisol stress response, diurnal rhythm, or cortisol awakening response (CAR)] in individuals with autism spectrum disorder (ASD) relative to controls. Thirdly, the evidence for an association between emotional and biological stress in ASD was reviewed.MethodMEDLINE, Cochrane Library, and SAGE journals were searched until December 2020. In this review, there were no limitations regarding age, sex, or intelligence quotient. Studies were only reviewed if results were compared with controls without a developmental disorder. Only salivary cortisol was considered as biological stress measure.ResultsThirty-one studies were reviewed. Significantly higher self- and parent-reported emotional stress levels were found in individuals with ASD compared to controls. Regarding biological stress, the few studies in adults reported comparable cortisol stress responses and rhythms between both groups. In children/adolescents with ASD relative to controls, an increased, blunted, or similar cortisol stress response was reported, whereas the CAR did not differ in most studies, and diurnal rhythm was described as blunted or similar. Most studies found no significant association between parent-reported emotional stress and biological stress in ASD.ConclusionsCurrent findings suggest that heightened emotional stress is a clinically significant factor in ASD. To unravel the cortisol response and rhythm, research in specific subgroups within the ASD spectrum is warranted, aiming at a higher frequency of cortisol measurements, preferably combined with momentary emotional stress measurements.     

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.